[ { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f1wet-5rp89", "eprint_status": "archive", "datestamp": "2023-12-08 20:56:57", "lastmod": "2024-01-09 22:23:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Godneeva-Baira", "name": { "family": "Godneeva", "given": "Baira" }, "orcid": "0009-0004-1662-8844" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei" }, "orcid": "0000-0002-6956-8257" } ] }, "title": "SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes", "ispublished": "pub", "full_text_status": "public", "keywords": "General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience", "note": "
\u00a9 2023, Godneeva et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
\n\nWe thank members of the Aravin and Fejes Toth labs for discussion. We thank Peiwei Chen for suggesting some of the experiments. We appreciate the help of Anastasiya Grebin with the experiments. We are grateful to Julius Brennecke, Gregory Hannon, Albert Courey, the Bloomington Stock Center, and the Vienna Drosophila Resource Center for providing fly stocks, Hugo Bellen for providing antibodies. We thank Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) for the help with sequencing, Giada Spigolon (Biological Imaging Facility, Caltech) for the help with microscopy, and Grace Shin for the help with HCR experiments. This work was supported by grants from the National Institutes of Health (R01 GM097363 to A.A.A. and R01 GM110217 to K.F.T. and R00 HD099316 to M.N.) and by the HHMI Faculty Scholar Award to A.A.A.
\n\nThe funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.
National Institutes of Health R01 GM097363 to Alexei Aravin.
National Institutes of Health R01 GM110217 to Katalin Fejes-Toth.
Howard Hughes Medical Institute Faculty Scholar Award to Alexei Aravin.
National Institutes of Health R00 HD099316 to Maria Ninova.
\n\nThe sequencing datasets have been deposited to the NCBI GEO archive under accession code GSE241375.
The following dataset was generated:
Godneeva B. 2023. SUMOylation of Bonus, the Drosophila homolog of Transcription Intermediary Factor 1, safeguards germline identity by recruiting repressive chromatin complexes to silence tissue-specific genes. NCBI Gene Expression Omnibus. GSE241375
\n\nBaira Godneeva, Conceptualization, Software, Formal analysis, Investigation, Visualization, Methodology, Writing \u2013 original draft; Maria Ninova, Conceptualization, Software, Formal analysis, Methodology, Writing \u2013 review and editing; Katalin Fejes-Toth, Alexei Aravin, Conceptualization, Formal analysis, Funding acquisition, Methodology, Writing \u2013 review and editing
\n\nNo competing interests declared.
", "abstract": "The conserved family of Transcription Intermediary Factors (TIF1) proteins consists of key transcriptional regulators that control transcription of target genes by modulating chromatin state. Unlike mammals that have four TIF1 members, Drosophila only encodes one member of the family, Bonus. Bonus has been implicated in embryonic development and organogenesis and shown to regulate several signaling pathways, however, its targets and mechanism of action remained poorly understood. We found that knockdown of Bonus in early oogenesis results in severe defects in ovarian development and in ectopic expression of genes that are normally repressed in the germline, demonstrating its essential function in the ovary. Recruitment of Bonus to chromatin leads to silencing associated with accumulation of the repressive H3K9me3 mark. We show that Bonus associates with the histone methyltransferase SetDB1 and the chromatin remodeler NuRD and depletion of either component releases Bonus-induced repression. We further established that Bonus is SUMOylated at a single site at its N-terminus that is conserved among insects and this modification is indispensable for Bonus's repressive activity. SUMOylation influences Bonus's subnuclear localization, its association with chromatin and interaction with SetDB1. Finally, we showed that Bonus SUMOylation is mediated by the SUMO E3-ligase Su(var)2\u201310, revealing that although SUMOylation of TIF1 proteins is conserved between insects and mammals, both the mechanism and specific site of modification is different in the two taxa. Together, our work identified Bonus as a regulator of tissue-specific gene expression and revealed the importance of SUMOylation as a regulator of complex formation in the context of transcriptional repression.
", "date": "2023-11-24", "date_type": "published", "publication": "eLife", "volume": "12", "publisher": "eLife Sciences Publications, Ltd", "pagerange": "RP89493", "issn": "2050-084X", "official_url": "https://authors.library.caltech.edu/records/f1wet-5rp89", "funders": { "items": [ { "grant_number": "R01 GM097363" }, { "grant_number": "R01 GM110217" }, {}, { "grant_number": "R00 HD099316" } ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/elife.89493", "pmcid": "PMC10672805", "primary_object": { "basename": "elife-89493-v1.pdf", "url": "https://authors.library.caltech.edu/records/f1wet-5rp89/files/elife-89493-v1.pdf" }, "related_objects": [ { "basename": "elife-89493-supp1.docx", "url": "https://authors.library.caltech.edu/records/f1wet-5rp89/files/elife-89493-supp1.docx" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Godneeva, Baira; Ninova, Maria; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/25eyv-y8h36", "eprint_status": "archive", "datestamp": "2023-12-08 20:26:45", "lastmod": "2024-01-09 22:23:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "name": { "family": "Godneeva", "given": "Baira" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Quan-Baiyi", "name": { "family": "Quan", "given": "Baiyi" }, "orcid": "0000-0001-6313-4274" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Impact of Germline Depletion of Bonus on Chromatin State in Drosophila Ovaries", "ispublished": "pub", "full_text_status": "public", "keywords": "General Medicine", "note": "\u00a9 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
\n\nWe thank members of the Aravin and Kulbachinskiy labs for discussion. We thank Andrey Kulbachinskiy, Maria Ninova, and Peiwei Chen for comments on the manuscript. We are grateful to the Bloomington Stock Center for providing fly stocks, and Hugo Bellen for providing the antibodies. We thank Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) for help with sequencing, and Giada Spigolon (Biological Imaging Facility, Caltech) for help with microscopy.
\n\nThis work was supported by grants from the National Institutes of Health (R01 GM097363 to A.A.A. and R01 GM110217 to K.F.T.) and by the HHMI Faculty Scholar Award to A.A.A.
\n\nB.G. and A.A.A. conceptualized the study. B.G. designed and performed experiments, data curation, and formal analysis, except LC-MS runs and raw data processing, which were performed at the Caltech PEL facility by B.G., B.Q., T.-F.C. and B.G. prepared figures and drafted the manuscript. B.G., K.F.T. and A.A.A. edited the manuscript. All authors have read and agreed to the published version of the manuscript.
\n\nThe data presented in this study are available from the corresponding author on reasonable request.
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cells12222629/s1, Figure S1: Average plot profiles of H3K27me3 (A), H3K27ac (B), and H3K9ac (C) over the gene body in control and Bon germline knockdown ovaries (BonusKD).
\n\nThe authors declare no conflict of interest.
", "abstract": "Gene expression is controlled via complex regulatory mechanisms involving transcription factors, chromatin modifications, and chromatin regulatory factors. Histone modifications, such as H3K27me3, H3K9ac, and H3K27ac, play an important role in controlling chromatin accessibility and transcriptional output. In vertebrates, the Transcriptional Intermediary Factor 1 (TIF1) family of proteins play essential roles in transcription, cell differentiation, DNA repair, and mitosis. Our study focused on Bonus, the sole member of the TIF1 family in Drosophila, to investigate its role in organizing epigenetic modifications. Our findings demonstrated that depleting Bonus in ovaries leads to a mild reduction in the H3K27me3 level over transposon regions and alters the distribution of active H3K9ac marks on specific protein-coding genes. Additionally, through mass spectrometry analysis, we identified novel interacting partners of Bonus in ovaries, such as PolQ, providing a comprehensive understanding of the associated molecular pathways. Furthermore, our research revealed Bonus's interactions with the Polycomb Repressive Complex 2 and its co-purification with select histone acetyltransferases, shedding light on the underlying mechanisms behind these changes in chromatin modifications.", "date": "2023-11", "date_type": "published", "publication": "Cells", "volume": "12", "number": "22", "publisher": "MDPI AG", "pagerange": "2629", "issn": "2073-4409", "official_url": "https://authors.library.caltech.edu/records/25eyv-y8h36", "funders": { "items": [ { "grant_number": "R01 GM097363" }, { "grant_number": "R01 GM110217" }, {} ] }, "local_group": { "items": [ { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.3390/cells12222629", "pmcid": "PMC10670193", "primary_object": { "basename": "cells-12-02629.pdf", "url": "https://authors.library.caltech.edu/records/25eyv-y8h36/files/cells-12-02629.pdf" }, "related_objects": [ { "basename": "cells-12-02629-s001.zip", "url": "https://authors.library.caltech.edu/records/25eyv-y8h36/files/cells-12-02629-s001.zip" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Godneeva, Baira; Fejes Toth, Katalin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/t4wqs-5xt29", "eprint_status": "archive", "datestamp": "2023-10-24 20:40:32", "lastmod": "2024-01-09 22:19:57", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "He-Peng", "name": { "family": "He", "given": "Peng" } }, { "id": "Kanrar-Nivedita", "name": { "family": "Kanrar", "given": "Nivedita" }, "orcid": "0000-0003-0047-951X" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Maternally inherited siRNAs initiate piRNA cluster formation", "ispublished": "pub", "full_text_status": "public", "keywords": "Cell Biology; Molecular Biology", "note": "\u00a9 2023 Elsevier.
\n\nWe thank members of the Aravin and Fejes Toth labs for discussion and comments. We thank Julius Brennecke for providing the Rhino antibody. We thank Igor Antoshechkin (Caltech) for help with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363 to A.A.A. and R01 GM110217 to K.F.T.) and by the HHMI Faculty Scholar Award to A.A.A.
\n\nY.L., K.F.T., and A.A.A. designed the experiments; Y.L. performed all experiments; N.K. helped to perform imaging and ChIP experiments; P.H. performed the computational analysis; Y.L. and P.H. analyzed the data; and Y.L., K.F.T., and A.A.A. wrote the paper.
\n\nThe authors declare no competing interests.
", "abstract": "PIWI-interacting RNAs (piRNAs) guide transposable element repression in animal germ lines. In Drosophila, piRNAs are produced from heterochromatic loci, called piRNA clusters, which act as information repositories about genome invaders. piRNA generation by dual-strand clusters depends on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a positive feedback loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed before cognate piRNAs are present remains unknown. Here, we report spontaneous de novo piRNA cluster formation from repetitive transgenic sequences. Cluster formation occurs over several generations and requires continuous trans-generational maternal transmission of small RNAs. We discovered that maternally supplied small interfering RNAs (siRNAs) trigger de novo cluster activation in progeny. In contrast, siRNAs are dispensable for cluster function after its establishment. These results reveal an unexpected interplay between the siRNA and piRNA pathways and suggest a mechanism for de novo piRNA cluster formation triggered by siRNAs.
", "date": "2023-10-23", "date_type": "published", "publication": "Molecular Cell", "publisher": "Cell Press", "issn": "1097-2765", "official_url": "https://authors.library.caltech.edu/records/t4wqs-5xt29", "funders": { "items": [ { "grant_number": "R01 GM097363" }, { "grant_number": "R01 GM110217" }, {} ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.molcel.2023.09.033", "resource_type": "article", "pub_year": "2023", "author_list": "Luo, Yicheng; He, Peng; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0d3a8-c8q83", "eprint_status": "archive", "datestamp": "2023-11-03 18:20:23", "lastmod": "2024-01-09 22:20:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Venkei-Zsolt-G", "name": { "family": "Venkei", "given": "Zsolt G." }, "orcid": "0000-0003-1282-849X" }, { "id": "Gainetdinov-Ildar", "name": { "family": "Gainetdinov", "given": "Ildar" }, "orcid": "0000-0003-1719-043X" }, { "id": "Bagci-Ayca", "name": { "family": "Bagci", "given": "Ayca" }, "orcid": "0000-0003-0828-555X" }, { "id": "Starostik-Margaret-R", "name": { "family": "Starostik", "given": "Margaret R." }, "orcid": "0000-0002-5274-2765" }, { "id": "Choi-Charlotte-P", "name": { "family": "Choi", "given": "Charlotte P." }, "orcid": "0000-0003-3649-6290" }, { "id": "Fingerhut-Jaclyn-M", "name": { "family": "Fingerhut", "given": "Jaclyn M." }, "orcid": "0000-0002-2347-0799" }, { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Balsara-Chiraag", "name": { "family": "Balsara", "given": "Chiraag" } }, { "id": "Whitfield-Troy-W", "name": { "family": "Whitfield", "given": "Troy W." }, "orcid": "0000-0002-2026-4201" }, { "id": "Bell-George-W", "name": { "family": "Bell", "given": "George W." } }, { "id": "Feng-Suhua", "name": { "family": "Feng", "given": "Suhua" } }, { "id": "Jacobsen-Steven-E", "name": { "family": "Jacobsen", "given": "Steven E." }, "orcid": "0000-0001-9483-138X" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kim-John-K", "name": { "family": "Kim", "given": "John K." }, "orcid": "0000-0002-4562-3872" }, { "id": "Zamore-Phillip-D", "name": { "family": "Zamore", "given": "Phillip D." }, "orcid": "0000-0002-4505-9618" }, { "id": "Yamashita-Yukiko-M", "name": { "family": "Yamashita", "given": "Yukiko M." }, "orcid": "0000-0001-5541-0216" } ] }, "title": "A maternally programmed intergenerational mechanism enables male offspring to make piRNAs from Y-linked precursor RNAs in Drosophila", "ispublished": "pub", "full_text_status": "public", "keywords": "Cell Biology", "note": "This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
\n\nWe thank the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank for reagents. We thank Z. Zhang and N. Lau for their helpful discussions and the Yamashita lab members for comments on the paper. The research was supported by the Howard Hughes Medical Institute (Y.M.Y., P.D.Z. and S.E.J.), National Institute of Health (NIH R01 HD109667 to J.K.K., R35 GM136275 to P.D.Z., R01GM097363 to A.A.A. and R35 GM130272 to S.E.J.) and the Whitehead Institute for Biomedical Research (Y.M.Y.).
\n\nThese authors contributed equally: Zsolt G. Venkei, Ildar Gainetdinov.
Z.G.V. and Y.M.Y. conceived the project. Z.G.V., I.G., S.E.J., J.K.K., P.D.Z. and Y.M.Y. designed experiments and interpreted the results. Z.G.V., I.G., A.B., C.B., J.M.F. and Y.M.Y. conducted experiments. Z.G.V., I.G., M.R.S., C.P.C., T.W.W., G.W.B. and S.F. analysed data. P.C. and A.A.A. contributed critical information in the course of the investigation. Z.G.V., I.G., Y.M.Y. and P.D.Z. wrote and edited the paper with the input from other authors. Y.M.Y. and P.D.Z. supervised the research.
\n\nSequencing data generated in this study have been deposited in the National Center for Biotechnology Information Short Read Archive database under accession code PRJNA879723. Fly genome sequence and annotation (build dm6/BDGP6.22 release 98) used in this study were downloaded from Ensembl at ftp://ftp.ensembl.org/pub/release-98/fasta/drosophila_melanogaster/ and ftp://ftp.ensembl.org/pub/release-98/gtf/drosophila_melanogaster/; fly rRNA sequences were downloaded from SILVA rRNA database at https://www.arb-silva.de/. Source data are provided with this paper. All other data supporting the findings of this study are available from the corresponding authors upon request.
\n\nCode used in this work is deposited at https://github.com/ildargv/Venkei_et_al_2023.
", "abstract": "In animals, PIWI-interacting RNAs (piRNAs) direct PIWI proteins to silence complementary targets such as transposons. In Drosophila and other species with a maternally specified germline, piRNAs deposited in the egg initiate piRNA biogenesis in the progeny. However, Y chromosome loci cannot participate in such a chain of intergenerational inheritance. How then can the biogenesis of Y-linked piRNAs be initiated? Here, using Suppressor of Stellate (Su(Ste)), a Y-linked Drosophila melanogaster piRNA locus as a model, we show that Su(Ste) piRNAs are made in the early male germline via 5\u2032-to-3\u2032 phased piRNA biogenesis initiated by maternally deposited 1360/Hoppel transposon piRNAs. Notably, deposition of Su(Ste) piRNAs from XXY mothers obviates the need for phased piRNA biogenesis in sons. Together, our study uncovers a developmentally programmed, intergenerational mechanism that allows fly mothers to protect their sons using a Y-linked piRNA locus.
", "date": "2023-10", "date_type": "published", "publication": "Nature Cell Biology", "volume": "25", "number": "10", "publisher": "Nature Publishing Group", "pagerange": "1495-1505", "issn": "1465-7392", "official_url": "https://authors.library.caltech.edu/records/0d3a8-c8q83", "funders": { "items": [ {}, { "grant_number": "R01 HD109667" }, { "grant_number": "R35 GM136275" }, { "grant_number": "R01GM097363" }, { "grant_number": "R35 GM130272" }, {} ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41556-023-01227-4", "pmcid": "PMC10567549", "primary_object": { "basename": "s41556-023-01227-4.pdf", "url": "https://authors.library.caltech.edu/records/0d3a8-c8q83/files/s41556-023-01227-4.pdf" }, "resource_type": "article", "pub_year": "2023", "author_list": "Venkei, Zsolt G.; Gainetdinov, Ildar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/q3emr-red92", "eprint_status": "archive", "datestamp": "2023-09-08 16:55:59", "lastmod": "2024-01-09 22:18:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Holmes-Hannah", "name": { "family": "Holmes", "given": "Hannah" } }, { "id": "Lomenick-Brett", "name": { "family": "Lomenick", "given": "Brett" }, "orcid": "0000-0002-5023-9998" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Pervasive SUMOylation of heterochromatin and piRNA pathway proteins", "ispublished": "pub", "full_text_status": "public", "keywords": "Genetics; Biochemistry, Genetics and Molecular Biology (miscellaneous)", "note": "\u00a9 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
\n\nWe thank former Caltech Protein Exploration Laboratory (PEL) members Dr. Michael Sweredoski and Dr. Annie Moradian for their advice on diGly proteomics, and Corinne Karalun (former laboratory assistant in M.N. laboratory, UCR), Hannah Ryon (former rotation student in K.F.T. laboratory, Caltech), and Matea Ibrahim (undergraduate student at UC Riverside) for assistance with WB, fly dissections, fixation, and genotyping. This work was supported by grants from the NIH (K99/R00 HD099316) to M.N.; the NIH (R01 GM097363) and the Howard Hughes Medical Institute Faculty Scholar Award to A.A.A.; and the NIH (R01 GM110217) and Ellison Medical Foundation Awards to K.F.T.
\n\nM.N., K.F.T., and A.A.A. conceptualized the proteomics study. M.N. designed and performed experiments, data curation, and formal analysis, except LC-MS/MS runs and raw data processing, which were performed at the Caltech PEL facility by B.L. H.H. performed GFP-Aub localization experiments. M.N. prepared figures and drafted the manuscript. M.N. and A.A.A. edited the manuscript.
\n\nThe mass spectrometry raw and processed data are deposited to the ProteomeXchange Consortium (https://www.ebi.ac.uk/pride/) via the PRIDE repository with the dataset identifier PRIDE: PXD037421 and are publicly available as of the date of publication. All original code is available at Zenodo: https://doi.org/10.5281/zenodo.7834381.
\n\nThe authors declare no competing interests.
", "abstract": "enome regulation involves complex protein interactions that are often mediated through post-translational modifications (PTMs). SUMOylation\u2014modification by the small ubiquitin-like modifier (SUMO)\u2014has been implicated in numerous essential processes in eukaryotes. In Drosophila, SUMO is required for viability and fertility, with its depletion from ovaries leading to heterochromatin loss and ectopic transposon and gene activation. Here, we developed a proteomics-based strategy to uncover the Drosophila ovarian \"SUMOylome,\" which revealed that SUMOylation is widespread among proteins involved in heterochromatin regulation and different aspects of the Piwi-interacting small RNA (piRNA) pathway that represses transposons. Furthermore, we show that SUMOylation of several piRNA pathway proteins occurs in a Piwi-dependent manner. Together, these data highlight broad implications of protein SUMOylation in epigenetic regulation and indicate novel roles of this modification in the cellular defense against genomic parasites. Finally, this work provides a resource for the study of SUMOylation in other biological contexts in the Drosophila model.
", "date": "2023-07-12", "date_type": "published", "publication": "Cell Genomics", "volume": "3", "number": "7", "publisher": "Cell Press", "pagerange": "100329", "issn": "2666-979X", "official_url": "https://authors.library.caltech.edu/records/q3emr-red92", "funders": { "items": [ { "grant_number": "K99/R00 HD099316" }, { "grant_number": "R01 GM097363" }, {}, { "grant_number": "R01 GM110217" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.xgen.2023.100329", "pmcid": "PMC10363806", "primary_object": { "basename": "main.pdf", "url": "https://authors.library.caltech.edu/records/q3emr-red92/files/main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2666979X23000976-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/q3emr-red92/files/1-s2.0-S2666979X23000976-mmc1.pdf" }, { "basename": "1-s2.0-S2666979X23000976-mmc2.xlsx", "url": "https://authors.library.caltech.edu/records/q3emr-red92/files/1-s2.0-S2666979X23000976-mmc2.xlsx" }, { "basename": "1-s2.0-S2666979X23000976-mmc3.xlsx", "url": "https://authors.library.caltech.edu/records/q3emr-red92/files/1-s2.0-S2666979X23000976-mmc3.xlsx" }, { "basename": "1-s2.0-S2666979X23000976-mmc4.xlsx", "url": "https://authors.library.caltech.edu/records/q3emr-red92/files/1-s2.0-S2666979X23000976-mmc4.xlsx" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Ninova, Maria; Holmes, Hannah; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/agq1f-sqr40", "eprint_id": 120753, "eprint_status": "archive", "datestamp": "2023-08-22 20:53:48", "lastmod": "2023-12-22 23:23:28", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Okhtienko-Anastasiia", "name": { "family": "Okhtienko", "given": "Anastasiia" } }, { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Panteleev-Vladimir", "name": { "family": "Panteleev", "given": "Vladimir" }, "orcid": "0000-0001-8643-5707" }, { "id": "Prostova-Maria", "name": { "family": "Prostova", "given": "Maria" }, "orcid": "0000-0001-5630-3471" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey-V", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Specific targeting of plasmids with Argonaute enables genome editing", "ispublished": "pub", "full_text_status": "public", "keywords": "Genetics", "note": "\u00a9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nWe thank Dr David Leach for bacterial strains and insightful discussions, Dr Gerry Smith for discussions on the mechanism of RecBCD, Dr Anton Kuzmenko for the recB-minus E. coli strain, Dr Aleksei Agapov for help with statistical analysis and figure preparation.\n\nAuthor contributions: Conceptualization: D.E., A.A. and A.K.; Supervision: D.E., A.K.; Investigation: D.E., A. Okhtienko, A. Olina, V.P., M.P.; Data analysis: A. Okhtienko, M.P., A.K., D.E.; Preparation of figures: A. Okhtienko, A. Olina; Writing and editing: A.K. with contribution from all the authors. \n\nThe authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.\n\nFUNDING: Russian Science Foundation [19-14-00359 (DNA interference assays)]; Russian Ministry of Science and Higher Education [075-15-2021-1062 (recombination assays)]. Funding for open access charge: Russian Science Foundation [19-14-00359]; Russian Ministry of Science and Higher Education [075-15-2021-1062]. \n\nDATA AVAILABILITY. All the data are available from the corresponding authors upon request. The results of smDNA sequencing and genomic DNA sequencing of E. coli strains after recombination are available from the Gene Expression Omnibus (GEO) database under accession number GSE200694. The code used for data analysis is available at the Zenodo repository at https://doi.org/10.5281/zenodo.7701080. \n\nConflict of interest statement. None declared.\n\nPublished - gkad191.pdf
Supplemental Material - gkad191_supplemental_file.pdf
", "abstract": "Prokaryotic Argonautes (pAgos) are programmable nucleases involved in cell defense against invading DNA. In vitro, pAgos can bind small single-stranded guide DNAs to recognize and cleave complementary DNA. In vivo, pAgos preferentially target plasmids, phages and multicopy genetic elements. Here, we show that CbAgo nuclease from Clostridium butyricum can be used for genomic DNA engineering in bacteria. We demonstrate that CbAgo loaded with plasmid-derived guide DNAs can recognize and cleave homologous chromosomal loci, and define the minimal length of homology required for this targeting. Cleavage of plasmid DNA at an engineered site of the I-SceI meganuclease increases guide DNA loading into CbAgo and enhances processing of homologous chromosomal loci. Analysis of guide DNA loading into CbAgo also reveals off-target sites of I-SceI in the Escherichia coli genome, demonstrating that pAgos can be used for highly sensitive detection of double-stranded breaks in genomic DNA. Finally, we show that CbAgo-dependent targeting of genomic loci with plasmid-derived guide DNAs promotes homologous recombination between plasmid and chromosomal DNA, depending on the catalytic activity of CbAgo. Specific targeting of plasmids with Argonautes can be used to integrate plasmid-encoded sequences into the chromosome thus enabling genome editing.", "date": "2023-05-08", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "51", "number": "8", "publisher": "Oxford University Press", "pagerange": "4086-4099", "id_number": "CaltechAUTHORS:20230411-764712100.9", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230411-764712100.9", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" }, { "agency": "Ministry of Science and Higher Education (Russia)", "grant_number": "075-15-2021-1062" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1093/nar/gkad191", "pmcid": "PMC10164558", "primary_object": { "basename": "gkad191.pdf", "url": "https://authors.library.caltech.edu/records/agq1f-sqr40/files/gkad191.pdf" }, "related_objects": [ { "basename": "gkad191_supplemental_file.pdf", "url": "https://authors.library.caltech.edu/records/agq1f-sqr40/files/gkad191_supplemental_file.pdf" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Esyunina, Daria; Okhtienko, Anastasiia; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k5ere-hfg82", "eprint_id": 121501, "eprint_status": "archive", "datestamp": "2023-08-22 20:48:26", "lastmod": "2023-12-22 23:22:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Agapov-Aleksei", "name": { "family": "Agapov", "given": "Aleksei" }, "orcid": "0000-0002-8662-8573" }, { "id": "Yudin-Denis", "name": { "family": "Yudin", "given": "Denis" }, "orcid": "0000-0002-4103-0543" }, { "id": "Sutormin-Dmitry", "name": { "family": "Sutormin", "given": "Dmitry" }, "orcid": "0000-0001-6834-4246" }, { "id": "Galivondzhyan-Alina", "name": { "family": "Galivondzhyan", "given": "Alina" }, "orcid": "0000-0002-8078-441X" }, { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Severinov-Konstantin", "name": { "family": "Severinov", "given": "Konstantin" }, "orcid": "0000-0001-9706-450X" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Bacterial Argonaute Proteins Aid Cell Division in the Presence of Topoisomerase Inhibitors in Escherichia coli", "ispublished": "pub", "full_text_status": "public", "keywords": "Infectious Diseases; Cell Biology; Microbiology (medical); Genetics; General Immunology and Microbiology; Ecology; Physiology", "note": "\u00a9 2023 Olina et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. \n\nWe thank Daria Esyunina for continued advice on this study and Phillip Zamore and Samson M. Jolly for helpful discussions. \n\nThis work was supported by the Russian Science Foundation (grant 19-14-00359 to Daria Esyunina, analysis of smDNA biogenesis and the effects of Cfx on DNA damage; grant 20-74-10127 to A.A., analysis of the effects of pAgos on replication termination). D.S. and A.G. were supported by a grant from the Ministry of Science and Higher Education of Russian Federation (agreement 075-10-2021-114; analysis of gyrase-induced DNA cleavage). \n\nWe declare no competing interests. \n\nAndrey Kulbachinskiy and Alexei A. Aravin conceived the study; Anna Olina performed experiments; Alina Galivondzhyan analyzed cell growth in the presence of Cfx; Aleksei Agapov and Dmitry Sutormin performed bioinformatic analysis of small DNA libraries; Denis Yudin made the original discovery of the chromosomal specificity of pAgos under supervision of Anton Kuzmenko and performed initial analysis of small DNAs; Anna Olina, Aleksei Agapov, and Dmitry Sutormin prepared the figures; and Andrey Kulbachinskiy and Dmitry Sutormin wrote the manuscript with contributions from all the authors. \n\nData availability: The smDNA sequencing data sets generated in this study are available from the Sequence Read Archive (SRA) database under BioProject number PRJNA878808. The code used for data analysis is available at the GitHub repository at https://github.com/AlekseiAgapov/SeAgo_LrAgo. All primary data are available from the corresponding author upon request.\n\nPublished - spectrum.04146-22.pdf
Supplemental Material - spectrum.04146-22-s0001.pdf
", "abstract": "Prokaryotic Argonaute (pAgo) proteins are guide-dependent nucleases that function in host defense against invaders. Recently, it was shown that TtAgo from Thermus thermophilus also participates in the completion of DNA replication by decatenating chromosomal DNA. Here, we show that two pAgos from cyanobacteria Synechococcus elongatus (SeAgo) and Limnothrix rosea (LrAgo) are active in heterologous Escherichia coli and aid cell division in the presence of the gyrase inhibitor ciprofloxacin, depending on the host double-strand break repair machinery. Both pAgos are preferentially loaded with small guide DNAs (smDNAs) derived from the sites of replication termination. Ciprofloxacin increases the amounts of smDNAs from the termination region and from the sites of genomic DNA cleavage by gyrase, suggesting that smDNA biogenesis depends on DNA replication and is stimulated by gyrase inhibition. Ciprofloxacin enhances asymmetry in the distribution of smDNAs around Chi sites, indicating that it induces double-strand breaks that serve as a source of smDNA during their processing by RecBCD. While active in E. coli, SeAgo does not protect its native host S. elongatus from ciprofloxacin. These results suggest that pAgo nucleases may help to complete replication of chromosomal DNA by promoting chromosome decatenation or participating in the processing of gyrase cleavage sites, and may switch their functional activities depending on the host species.", "date": "2023-05", "date_type": "published", "publication": "Microbiology Spectrum", "volume": "11", "number": "3", "publisher": "American Society for Microbiology", "pagerange": "Art. No. 04146-22", "id_number": "CaltechAUTHORS:20230523-606187700.7", "issn": "2165-0497", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230523-606187700.7", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" }, { "agency": "Russian Science Foundation", "grant_number": "20-74-10127" }, { "agency": "Ministry of Science and Higher Education (Russia)", "grant_number": "075-10-2021-114" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1128/spectrum.04146-22", "pmcid": "PMC10269773", "primary_object": { "basename": "spectrum.04146-22.pdf", "url": "https://authors.library.caltech.edu/records/k5ere-hfg82/files/spectrum.04146-22.pdf" }, "related_objects": [ { "basename": "spectrum.04146-22-s0001.pdf", "url": "https://authors.library.caltech.edu/records/k5ere-hfg82/files/spectrum.04146-22-s0001.pdf" } ], "resource_type": "article", "pub_year": "2023", "author_list": "Olina, Anna; Agapov, Aleksei; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/e6s90-gzh58", "eprint_id": 120333, "eprint_status": "archive", "datestamp": "2023-08-20 08:33:03", "lastmod": "2023-12-13 16:37:54", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Agapov-Aleksei", "name": { "family": "Agapov", "given": "Aleksei" }, "orcid": "0000-0002-8662-8573" }, { "id": "Yudin-Denis", "name": { "family": "Yudin", "given": "Denis" }, "orcid": "0000-0002-4103-0543" }, { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey-V", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Bacterial Argonaute proteins aid cell division in the presence of topoisomerase inhibitors in Escherichia coli", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank Daria Esyunina for continued advice on this study, Phillip Zamore, Samson M. Jolly and Dmitry Sutormin for helpful discussions. This work was supported by grant 19-14-00359 of the Russian Science Foundation to Daria Esyunina. The authors declare no competing interests. \n\nAUTHOR CONTRIBUTIONS. Andrey Kulbachinskiy and Alexei Aravin conceived the study, Anna Olina performed experiments, Aleksei Agapov performed bioinformatic analysis of small DNA libraries, Denis Yudin made the original discovery of the chromosomal specificity of pAgos under supervision of Anton Kuzmenko and performed initial analysis of small DNAs, Anna Olina and Aleksei Agapov prepared the figures, Andrey Kulbachinskiy wrote the manuscript with contributions from all the authors. \n\nDATA AVAILABILITY. The smDNA sequencing datasets generated in this study are available from the Sequence Read Archive (SRA) database under bioproject number PRJNA878808. The code used for data analysis is available at the GitHub repository at https://github.com/AlekseiAgapov/SeAgo_LrAgo. All primary data are available from the corresponding author upon request.\n\nSubmitted - 2022.09.13.507849v2.full.pdf
Supplemental Material - media-1.pdf
", "abstract": "Prokaryotic Argonaute (pAgo) proteins are guide-dependent nucleases that function in host defense against invaders. Recently, it was shown that TtAgo from Thermus thermophilus also participates in the completion of DNA replication by decatenating chromosomal DNA. Here, we show that two pAgos from cyanobacteria Synechococcus elongatus (SeAgo) and Limnothrix roseae (LrAgo) act as DNA-guided DNA nucleases in Escherichia coli and aid cell division in the presence of the gyrase inhibitor ciprofloxacin. Both pAgos are preferentially loaded with small DNA guides derived from the sites of replication termination. The amount of pAgo-associated small DNAs (smDNAs) from the termination sites is increased in the presence ciprofloxacin, suggesting that smDNA biogenesis depends on DNA replication and is stimulated by gyrase inhibition. Ciprofloxacin also enhances asymmetry in the distribution of smDNAs around Chi-sites, indicating that it induces double-strand breaks that serve as a source of smDNA during their processing by RecBCD. While active in E. coli, SeAgo does not protect its native host S. elongatus from ciprofloxacin. These results suggest that pAgo nucleases help to complete replication of chromosomal DNA by targeting the sites of termination, and may switch their functional activities when expressed in different host species.", "date": "2023-03-28", "date_type": "published", "id_number": "CaltechAUTHORS:20230322-367204000.18", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-367204000.18", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.09.13.507849", "primary_object": { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/e6s90-gzh58/files/media-1.pdf" }, "related_objects": [ { "basename": "2022.09.13.507849v2.full.pdf", "url": "https://authors.library.caltech.edu/records/e6s90-gzh58/files/2022.09.13.507849v2.full.pdf" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Olina, Anna; Agapov, Aleksei; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/x0962-2a116", "eprint_id": 120334, "eprint_status": "archive", "datestamp": "2023-08-20 08:32:09", "lastmod": "2023-12-13 16:37:32", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Venkei-Zsolt-G", "name": { "family": "Venkei", "given": "Zsolt G." }, "orcid": "0000-0003-1282-849X" }, { "id": "Gainetdinov-Ildar", "name": { "family": "Gainetdinov", "given": "Ildar" }, "orcid": "0000-0003-1719-043X" }, { "id": "Starostik-Margaret-R", "name": { "family": "Starostik", "given": "Margaret R." }, "orcid": "0000-0002-5274-2765" }, { "id": "Choi-Charlotte-P", "name": { "family": "Choi", "given": "Charlotte P." }, "orcid": "0000-0003-3649-6290" }, { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Balsara-Chiraag", "name": { "family": "Balsara", "given": "Chiraag" } }, { "id": "Whitfield-Troy-W", "name": { "family": "Whitfield", "given": "Troy W." }, "orcid": "0000-0002-2026-4201" }, { "id": "Bell-George-W", "name": { "family": "Bell", "given": "George W." } }, { "id": "Feng-Suhua", "name": { "family": "Feng", "given": "Suhua" }, "orcid": "0000-0002-9963-9079" }, { "id": "Jacobsen-Steven-E", "name": { "family": "Jacobsen", "given": "Steven E." }, "orcid": "0000-0001-9483-138X" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kim-John-K", "name": { "family": "Kim", "given": "John K." } }, { "id": "Zamore-Philip-D", "name": { "family": "Zamore", "given": "Philip D." }, "orcid": "0000-0002-4505-9618" }, { "id": "Yamashita-Yukiko-M", "name": { "family": "Yamashita", "given": "Yukiko M." }, "orcid": "0000-0001-5541-0216" } ] }, "title": "Drosophila Males Use 5\u2032-to-3\u2032 Phased Biogenesis to Make Stellate-silencing piRNAs that Lack Homology to Maternally Deposited piRNA Guides", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. \n\nWe thank the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank for reagents. We thank Zhao Zhang and Nelson Lau for their helpful discussions, and the Yamashita lab members for comments on the manuscript. The research was supported by the Howard Hughes Medical Institute (YMY, PDZ, SEJ), National Institute of Health (NIH R01 HD109667 to JKK, R35 GM136275 to PDZ, R01GM097363 to \nAAA and R35 GM130272 to SEJ), and the Whitehead Institute for Biomedical Research (YMY). \n\nAuthor contributions. ZGV and YMY conceived the project. ZV, IG, CB and YMY conducted experiments. ZGV, IG, YMY, PDZ designed experiments and interpreted the results. ZGV, IG, MRS, CPC, JKK, TWW, and BWB conducted bioinformatics analysis. PC and AA contributed critical information in the course of the investigation. ZGV, IG, YMY, PDZ wrote and edited the manuscript with the inputs from other authors. YMY and PDZ supervised the research. \n\nData Availability. Sequencing data are available from the National Center for Biotechnology Information Small Read Archive using accession number PRJNA879723.\n\nSubmitted - 2022.09.12.507655v1.full.pdf
Supplemental Material - media-1.pdf
", "abstract": "PIWI-interacting RNAs (piRNAs) direct PIWI proteins to silence complementary targets such as transposons. In animals with a maternally specified germline, e.g. Drosophila melanogaster, maternally deposited piRNAs initiate piRNA biogenesis in the progeny. Normal fertility in D. melanogaster males requires repression of tandemly repeated Stellate genes by piRNAs from Suppressor of Stellate [Su(Ste)]. Because the Su(Ste) loci are on the Y chromosome, Su(Ste) piRNAs are not deposited in oocytes. How the male germline produces Su(Ste) piRNAs in the absence of maternally deposited Su(Ste) piRNAs is unknown. Here, we show that Su(Ste) piRNAs are made in the early male germline via 5\u2032-to-3\u2032 phased piRNA biogenesis triggered by maternally deposited 1360/Hoppel transposon piRNAs. Strikingly, deposition of Su(Ste) piRNAs from XXY mothers obviates the need for phased piRNA biogenesis in sons. Together, our study uncovers the developmentally programmed mechanism that allows fly mothers to protect their sons using a Y-linked piRNA locus.", "date": "2023-03-28", "date_type": "published", "id_number": "CaltechAUTHORS:20230322-367225000.19", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-367225000.19", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 HD109667" }, { "agency": "NIH", "grant_number": "R35 GM136275" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R35 GM130272" }, { "agency": "Whitehead Institute for Biomedical Research" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.09.12.507655", "primary_object": { "basename": "2022.09.12.507655v1.full.pdf", "url": "https://authors.library.caltech.edu/records/x0962-2a116/files/2022.09.12.507655v1.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/x0962-2a116/files/media-1.pdf" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Venkei, Zsolt G.; Gainetdinov, Ildar; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z488b-x9s48", "eprint_id": 120339, "eprint_status": "archive", "datestamp": "2023-08-20 08:31:42", "lastmod": "2023-12-13 16:37:52", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-Lidiya", "name": { "family": "Lisitskaya", "given": "Lidiya" }, "orcid": "0000-0002-5283-7983" }, { "id": "Kropocheva-Ekaterina", "name": { "family": "Kropocheva", "given": "Ekaterina" } }, { "id": "Agapov-Aleksei", "name": { "family": "Agapov", "given": "Aleksei" }, "orcid": "0000-0002-8662-8573" }, { "id": "Prostova-Maria", "name": { "family": "Prostova", "given": "Maria" }, "orcid": "0000-0001-5630-3471" }, { "id": "Panteleev-Vladimir", "name": { "family": "Panteleev", "given": "Vladimir" } }, { "id": "Yudin-Denis", "name": { "family": "Yudin", "given": "Denis" }, "orcid": "0000-0002-4103-0543" }, { "id": "Ryazansky-Sergey", "name": { "family": "Ryazansky", "given": "Sergey" }, "orcid": "0000-0002-3171-2997" }, { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Kulbachinskiy-Andrey-V", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Bacterial Argonaute nucleases reveal different modes of DNA targeting in vitro and in vivo", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank Dr. David Leach and Dr. Gerry Smith for insightful discussions, Dr. Anna Olina for help in preparation of smDNA libaries. \n\nThis study was supported in part by the Russian Science Foundation (grant 20-74-10127 to AA, analysis of in vitro activities of pAgos; grant 19-14-00359 to DE, analysis of genomic DNA targeting by pAgos). \n\nData Availability. The smDNA sequencing datasets generated in this study are available from the Sequence Read Archive (SRA) database under accession numbers PRJNA827032 and PRJNA827167. The code used for data analysis is available at the GitHub repository at https://github.com/AlekseiAgapov/5pAgos. The genomic sequence of phage P1 used in the experiments is available from GenBank under accession number OP279344. All primary data are available from the corresponding author upon request. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.09.09.507302v1.full.pdf
Supplemental Material - media-1.pdf
", "abstract": "Prokaryotic Argonaute proteins (pAgos) are homologs of eukaryotic Argonautes (eAgos) that were similarly proposed to play a role in cell defense against invaders. However, pAgos are much more diverse than eAgos and very little is known about their functional activity and target specificity in vivo. Here, we describe five pAgo proteins from mesophilic bacteria that act as DNA-guided DNA endonucleases and analyze their ability to target chromosomal and invader DNA. In vitro, the analyzed proteins use small guide DNAs for precise cleavage of single-stranded DNA at a wide range of temperatures. Upon their expression in Escherichia coli, all five pAgos are loaded with small DNAs preferentially produced from plasmid DNA and from chromosomal regions of replication termination. One of the tested pAgos, EmaAgo from Exiguobacterium marinum can induce DNA interference between multicopy sequences resulting in targeted processing of homologous plasmid and chromosomal loci. EmaAgo also protects bacteria from bacteriophage infection and is preferentially loaded with phage guide DNAs suggesting that the ability of pAgos to target multicopy elements may be crucial for their protective function. The wide spectrum of pAgo activities suggests that they may have diverse functions in vivo and paves the way for their use in biotechnology.", "date": "2023-03-27", "date_type": "published", "id_number": "CaltechAUTHORS:20230322-367657000.25", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-367657000.25", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "20-74-10127" }, { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.09.09.507302", "primary_object": { "basename": "2022.09.09.507302v1.full.pdf", "url": "https://authors.library.caltech.edu/records/z488b-x9s48/files/2022.09.09.507302v1.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/z488b-x9s48/files/media-1.pdf" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Lisitskaya, Lidiya; Kropocheva, Ekaterina; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/14wtz-2s519", "eprint_id": 120307, "eprint_status": "archive", "datestamp": "2023-08-20 08:41:43", "lastmod": "2023-12-22 23:41:29", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Genetic control of a sex-specific piRNA program", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank Grace YC Lee, Felipe Karam Teixeira, Justin Blumenstiel, Katalin Fejes Toth, and members of the Aravin Laboratory for discussion, Jim Kennison for advice on sex chromosome nondisjunction, Mark Van Doren and Helen Salz for advice on sex determination, and Yukiko Yamashita for sharing unpublished results. We thank Angela Stathopoulos, Ellen Rothenberg, and Henry Chung for comments on the manuscript. We are grateful to Liz Gavis, Bloomington Drosophila Stock Center and Vienna Drosophila Resource Center for fly lines. We appreciate the help of Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) with sequencing, the help of Fan Gao (Bioinformatics Resource Center, Caltech) with bioinformatic analysis, the help of Grace Shin (Molecular Technologies, Caltech) with in situ HCR, and the help of Giada Spigolon and Andres Collazo (Biological Imaging Facility, Caltech) with microscopy. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to A.A.A. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.10.25.513766v1.full.pdf
", "abstract": "Sexually dimorphic traits in morphologies are widely studied, but those in essential molecular pathways remain largely unexplored. Previous work showed substantial sex differences in Drosophila gonadal piRNAs, which guide PIWI proteins to silence selfish genetic elements thereby safeguarding fertility. However, the genetic control mechanisms of piRNA sexual dimorphism remain unknown. Here, we showed that most sex differences in the piRNA program originate from the germline rather than gonadal somatic cells. Building on this, we dissected the contribution of sex chromosome and cellular sexual identity towards the sex-specific germline piRNA program. We found that the presence of the Y chromosome is sufficient to recapitulate some aspects of the male piRNA program in a female cellular environment. Meanwhile, sexual identity controls the sexually divergent piRNA production from X-linked and autosomal loci, revealing a crucial input from sex determination into piRNA biogenesis. Sexual identity regulates piRNA biogenesis through Sxl and this effect is mediated in part through chromatin proteins Phf7 and Kipferl. Together, our work delineated the genetic control of a sex-specific piRNA program, where sex chromosome and sexual identity collectively sculpt an essential molecular trait.", "date": "2023-03-23", "date_type": "published", "id_number": "CaltechAUTHORS:20230322-101505000.10", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-101505000.10", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Millard-and-Muriel-Jacobs-Genetics-and-Genomics-Laboratory" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.10.25.513766", "primary_object": { "basename": "2022.10.25.513766v1.full.pdf", "url": "https://authors.library.caltech.edu/records/14wtz-2s519/files/2022.10.25.513766v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2023", "author_list": "Chen, Peiwei and Aravin, Alexei A." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5nhg8-ews92", "eprint_id": 116301, "eprint_status": "archive", "datestamp": "2023-08-20 08:26:28", "lastmod": "2023-12-13 16:50:10", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Lomenick-Brett", "name": { "family": "Lomenick", "given": "Brett" }, "orcid": "0000-0002-5023-9998" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes-T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Pervasive SUMOylation of heterochromatin and piRNA pathway proteins", "ispublished": "unpub", "full_text_status": "public", "keywords": "SUMO, piRNAs, heterochromatin, transposons, proteomics", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank former Caltech Protein Exploration Laboratory (PEL) members Dr. Michael Sweredoski and Dr. Annie Moradian for their advice on diGly proteomics, and Corinne Karalun (former laboratory assistant in MN laboratory, UCR), Hannah Ryon (former rotation student in KFT laboratory, Caltech), Hannah Holmes and Matea Ibrahim (undergraduate students in UC Riverside) for assistance with Western Blotting, fly dissections and genotyping. This work was supported by grants from the NIH (K99/R00 HD099316) to MN; the NIH (R01 GM097363), the Ministry of Education and Science of the Russian Federation (14.W03.31.0007), and the Packard Fellowship Awards to AAA, and the NIH (R01GM110217) and Ellison Medical Foundation Awards to KFT. \n\nAuthors contributions. MN, KFT and AAA conceptualized the proteomics study. MN designed and performed experiments, data curation and formal analysis, except LC-MS/MS runs and raw data processing which were performed at the Caltech PEL facility by BL. MN prepared figures and drafted the manuscript. MN and AAA edited the manuscript. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.08.15.504007v2.full.pdf
Supplemental Material - media-1.pdf
", "abstract": "Genome regulation involves complex and highly regulated protein interactions that are often mediated through post-translational modifications (PTMs). SUMOylation - the covalent attachment of the small ubiquitin-like modifier (SUMO) - is a conserved PTM in eukaryotes that has been implicated in a number of essential processes such as nuclear import, DNA damage repair, transcriptional control, and chromatin organization. In Drosophila, SUMO is essential for viability and its depletion from the female germline causes infertility associated with global loss of heterochromatin, and illicit upregulation of transposons and lineage-inappropriate genes. However, the specific targets of SUMO and its mechanistic role in different cellular pathways are still poorly understood. Here, we developed a proteomics-based strategy to characterize the SUMOylated proteome in Drosophila that allowed us to identify ~1500 SUMO sites in 843 proteins in the fly ovary. A high confidence set of SUMOylated proteins is highly enriched in factors involved in heterochromatin regulation and the piRNA pathway that represses transposons. Furthermore, SUMOylation of several piRNA pathway proteins occurs in a Piwi-dependent manner, indicating a functional implication of this modification in the cellular response to transposon activity. Together, these data highlight the impact of SUMOylation on epigenetic regulation and reveal an unexpectedly broad role of the SUMO pathway in the cellular defense against genomic parasites. Finally, this work provides a valuable resource and a system that can be adapted to the study of SUMOylation in other Drosophila tissues.", "date": "2022-08-16", "date_type": "published", "id_number": "CaltechAUTHORS:20220816-201512000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220816-201512000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99/R00 HD099316" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "NIH", "grant_number": "R01 GM110217" }, { "agency": "Ellison Medical Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.08.15.504007", "primary_object": { "basename": "2022.08.15.504007v2.full.pdf", "url": "https://authors.library.caltech.edu/records/5nhg8-ews92/files/2022.08.15.504007v2.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/5nhg8-ews92/files/media-1.pdf" } ], "resource_type": "monograph", "pub_year": "2022", "author_list": "Ninova, Maria; Lomenick, Brett; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qr97x-p2k42", "eprint_id": 116302, "eprint_status": "archive", "datestamp": "2023-08-22 17:18:47", "lastmod": "2023-12-22 23:23:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-Lidiya", "name": { "family": "Lisitskaya", "given": "Lidiya" }, "orcid": "0000-0002-5283-7983" }, { "id": "Shin-Yeonoh", "name": { "family": "Shin", "given": "Yeonoh" }, "orcid": "0000-0001-9718-2995" }, { "id": "Agapov-Aleksei", "name": { "family": "Agapov", "given": "Aleksei" }, "orcid": "0000-0002-8662-8573" }, { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Kropocheva-Ekaterina", "name": { "family": "Kropocheva", "given": "Ekaterina" }, "orcid": "0000-0001-8895-0577" }, { "id": "Ryazansky-Sergei", "name": { "family": "Ryazansky", "given": "Sergei" }, "orcid": "0000-0002-3171-2997" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Murakami-Katsuhiko-S", "name": { "family": "Murakami", "given": "Katsuhiko S." }, "orcid": "0000-0003-2244-0501" }, { "id": "Kulbachinskiy-Andrey-V", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Programmable RNA targeting by bacterial Argonaute nucleases with unconventional guide binding and cleavage specificity", "ispublished": "pub", "full_text_status": "public", "keywords": "General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary", "note": "\u00a9 The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 14 June 2022. Accepted 15 July 2022. Published 08 August 2022. \n\nWe thank the X-ray crystallography facility at Pennsylvania State University for screening crystallization conditions and Macromolecular X-ray science staff at the Cornell High Energy Synchrotron Source (MacCHESS) for supporting the crystallographic data collection, Dr. Alexandra Kulikova and Dr. Vladimir Mitkevich for analysis of protein thermal stability, Dr. Mayya Petrova for help with bacterial strains, Dr. Alexei Kotov for help with confocal microscopy. This study was supported in part by the Russian Science Foundation (grant 20-74-10127 to A. Agapov, analysis of nucleic acid specificity of pAgos; grant 22-14-00182 to A.K., analysis of mutant variants of pAgos) and National Institutes of Health (R35 GM131860 to KSM, structural analysis). \n\nContributions. A.A.A., D.E., K.S.M., and A.K. conceptualized the study. L.L., A.A., A.O., and E.K. designed and performed biochemical experiments, Y.S. performed crystallization and X-ray diffraction studies, Y.S. and K.S.M. performed structural analysis, S.R. performed bioinformatic analysis, A.K. and K.S.M. wrote the manuscript with input from all coauthors. \n\nData availability. The data that support this study are available from the corresponding authors upon request. The coordinates are deposited in the Protein Data Bank with PDB accession codes 7R8F (native PliAgo), 7R8G (PliAgo-OH-gDNA complex), 7R8H (PliAgo-P-gDNA complex), 7R8J (PliAgo-P-gDNA-Mg2+ complex) and 7R8K (SeMet PliAgo). Source data are provided with this paper. \n\nThe authors declare no competing interests. \n\nPeer review information. Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work. Peer reviewer reports are available.\n\nPublished - s41467-022-32079-5.pdf
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Supplemental Material - 41467_2022_32079_MOESM6_ESM.zip
", "abstract": "Argonaute proteins are programmable nucleases that have defense and regulatory functions in both eukaryotes and prokaryotes. All known prokaryotic Argonautes (pAgos) characterized so far act on DNA targets. Here, we describe a new class of pAgos that uniquely use DNA guides to process RNA targets. The biochemical and structural analysis of Pseudooceanicola lipolyticus pAgo (PliAgo) reveals an unusual organization of the guide binding pocket that does not rely on divalent cations and the canonical set of contacts for 5'-end interactions. Unconventional interactions of PliAgo with the 5'-phosphate of guide DNA define its new position within pAgo and shift the site of target RNA cleavage in comparison with known Argonautes. The specificity for RNA over DNA is defined by ribonucleotide residues at the cleavage site. The analysed pAgos sense mismatches and modifications in the RNA target. The results broaden our understanding of prokaryotic defense systems and extend the spectrum of programmable nucleases with potential use in RNA technology.", "date": "2022-08-08", "date_type": "published", "publication": "Nature Communications", "volume": "13", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 4624", "id_number": "CaltechAUTHORS:20220816-373347000", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220816-373347000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "20-74-10127" }, { "agency": "Russian Science Foundation", "grant_number": "22-14-00182" }, { "agency": "NIH", "grant_number": "R35 GM131860" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41467-022-32079-5", "pmcid": "PMC9360449", "primary_object": { "basename": "41467_2022_32079_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM2_ESM.pdf" }, "related_objects": [ { "basename": "41467_2022_32079_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM3_ESM.pdf" }, { "basename": "41467_2022_32079_MOESM4_ESM.mp4", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM4_ESM.mp4" }, { "basename": "41467_2022_32079_MOESM5_ESM.pdf", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM5_ESM.pdf" }, { "basename": "41467_2022_32079_MOESM6_ESM.zip", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM6_ESM.zip" }, { "basename": "s41467-022-32079-5.pdf", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/s41467-022-32079-5.pdf" }, { "basename": "41467_2022_32079_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/qr97x-p2k42/files/41467_2022_32079_MOESM1_ESM.pdf" } ], "resource_type": "article", "pub_year": "2022", "author_list": "Lisitskaya, Lidiya; Shin, Yeonoh; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/7dr7j-6zx71", "eprint_id": 114369, "eprint_status": "archive", "datestamp": "2023-08-20 07:30:58", "lastmod": "2023-12-13 16:38:16", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Okhtienko-Anastasiia", "name": { "family": "Okhtienko", "given": "Anastasiia" } }, { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Prostova-Maria", "name": { "family": "Prostova", "given": "Maria" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Specific targeting of plasmids with Argonaute enables genome editing", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nThis version posted April 14, 2022. \n\nWe thank Dr. David Leach for insightful discussions, Dr. Aleksei Agapov for help with figure preparation. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.04.14.488398v1.full.pdf
", "abstract": "Prokaryotic Argonautes (pAgos) are programmable nucleases involved in cell defense against invading DNA. Recent studies showed that pAgos can bind small single-stranded guide DNAs (gDNAs) to recognize and cleave complementary DNA in vitro. In vivo pAgos preferentially target plasmids, phages and multicopy genetic elements. Here, we reveal that CbAgo nuclease from Clostridium butyricum can be used for genomic DNA cleavage and engineering in bacteria. CbAgo-dependent targeting of genomic loci with plasmid-derived gDNAs promotes recombination between plasmid and chromosomal DNA. Efficient genome cleavage and recombineering depends on the catalytic activity of CbAgo, its interactions with gDNAs, and the extent of homology between plasmid and chromosomal sequences. Specific targeting of plasmids with Argonautes can be used to integrate plasmid-encoded sequences into the chromosome thus enabling genome editing. One-Sentence SummaryProkaryotic Argonaute nuclease induces DNA interference between plasmid and chromosomal DNA to promote genome recombineering.", "date": "2022-04-19", "date_type": "published", "id_number": "CaltechAUTHORS:20220419-766504700", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220419-766504700", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.04.14.488398", "primary_object": { "basename": "2022.04.14.488398v1.full.pdf", "url": "https://authors.library.caltech.edu/records/7dr7j-6zx71/files/2022.04.14.488398v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Esyunina, Daria; Okhtienko, Anastasiia; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n27yg-r4a52", "eprint_id": 113377, "eprint_status": "archive", "datestamp": "2023-08-20 06:59:42", "lastmod": "2023-12-13 16:50:02", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "He-Peng", "name": { "family": "He", "given": "Peng" } }, { "id": "Kanrar-Nivedita", "name": { "family": "Kanrar", "given": "Nivedita" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Maternally inherited siRNAs initiate piRNA cluster formation", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank members of the Aravin and Fejes Toth labs for discussion and comments. We thank Julius Brennecke for providing the Rhino antibody. We thank Igor Antoshechkin (Caltech) for help with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to AAA. \n\nAuthor Contributions. Y.L., K.F.T. and A.A.A. designed experiments. Y.L. performed all experiments; N.K. helped to perform imaging and ChIP experiments; P.H. performed the computational analysis; Y.L. and P.H. analyzed the data; Y.L., K.F.T. and A.A.A. wrote the paper. \n\nData availability Libraries generated from this study are deposited in GEO under accession codes GSE193091. The scripts are available on GitHub: https://github.com/brianpenghe/Luo_2021_piRNA. Pol ll ChIP-seq data analyzed in this study were from GSE43829 (Le Thomas et al., 2013) and GSE97719 (Andersen et al., 2017). \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.02.08.479612v1.full.pdf
", "abstract": "PIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals. In Drosophila, piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as a repositories of information about genome invaders. piRNA generation by dual-strand clusters depend on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed initially, before cognate piRNAs are present, remained unknown. Here we report spontaneous de novo formation of a piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. We discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for cluster function after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggest a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs.", "date": "2022-02-10", "date_type": "published", "id_number": "CaltechAUTHORS:20220210-639875000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220210-639875000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.02.08.479612", "primary_object": { "basename": "2022.02.08.479612v1.full.pdf", "url": "https://authors.library.caltech.edu/records/n27yg-r4a52/files/2022.02.08.479612v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Luo, Yicheng; He, Peng; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rts0b-jbc96", "eprint_id": 111591, "eprint_status": "archive", "datestamp": "2023-08-20 05:32:29", "lastmod": "2023-12-22 23:13:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Transposon-taming piRNAs in the germline: Where do they come from?", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2021 Published by Elsevier Inc. \n\nAvailable online 7 October 2021.", "abstract": "Mutations in the piRNA pathway protein components lead to transposon activation and fertility defects. In contrast, Gebert et al., (2021) saw no defects in transposon silencing or fertility when they deleted three large germline piRNA clusters in D. melanogaster.", "date": "2021-10-07", "date_type": "published", "publication": "Molecular Cell", "volume": "81", "number": "19", "publisher": "Cell Press", "pagerange": "3884-3885", "id_number": "CaltechAUTHORS:20211021-212935040", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211021-212935040", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.molcel.2021.09.017", "resource_type": "article", "pub_year": "2021", "author_list": "Chen, Peiwei and Aravin, Alexei A." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tcp03-tva18", "eprint_id": 105114, "eprint_status": "archive", "datestamp": "2023-08-20 05:02:06", "lastmod": "2023-12-22 23:41:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "RDC complex executes a dynamic piRNA program during Drosophila spermatogenesis to safeguard male fertility", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived: November 1, 2020; Accepted: May 10, 2021; Published: September 2, 2021. \n\nWe are grateful to Xin Chen, Peter Andersen, William Theurkauf, Trudi Sch\u00fcpbach, Paul Lasko, Elena Pasyukova and three Drosophila Stock Centers (Bloomington, Vienna, Kyoto) for fly stocks. We thank Katalin Fejes Toth and members of Aravin lab for discussion and comments. We appreciate the help of Maria Ninova and Fan Gao (Bioinformatics Resource Center, Caltech) with bioinformatics analysis, the help of Grace Shin and Maayan Schwarzkopf with HCR experiments, the help of Giada Spigolon and Andres Collazo (Biological Imaging Facility, Caltech) with microscopy, and the help of Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) with sequencing. \n\nData Availability Statement: All data are available within the manuscript except for the sequencing data, which is available at NCBI SRA (accession number: PRJNA646006). \n\nThis work was supported by the Howard Hughes Medical Institute Faculty Scholar Award (https://www.hhmi.org) and the National Institutes of Health R01 GM097363 (https://www.nih.gov) to AAA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. \n\nAuthor Contributions: \nConceptualization: Peiwei Chen, Alexei A. Aravin.\nData curation: Peiwei Chen, Alexei A. Aravin.\nFormal analysis: Peiwei Chen, Alexei A. Aravin.\nFunding acquisition: Alexei A. Aravin.\nInvestigation: Peiwei Chen, Yicheng Luo.\nMethodology: Peiwei Chen, Alexei A. Aravin.\nProject administration: Peiwei Chen, Alexei A. Aravin.\nResources: Peiwei Chen, Alexei A. Aravin.\nSoftware: Peiwei Chen, Alexei A. Aravin.\nSupervision: Peiwei Chen, Alexei A. Aravin.\nValidation: Peiwei Chen, Yicheng Luo, Alexei A. Aravin.\nVisualization: Peiwei Chen, Alexei A. Aravin.\nWriting \u2013 original draft: Peiwei Chen, Alexei A. Aravin.\nWriting \u2013 review & editing: Peiwei Chen, Alexei A. Aravin. \n\nThe authors have declared that no competing interests exist.\n\nPublished - journal.pgen.1009591.pdf
Submitted - 2020.08.25.266643v1.full.pdf
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", "abstract": "piRNAs are small non-coding RNAs that guide the silencing of transposons and other targets in animal gonads. In Drosophila female germline, many piRNA source loci dubbed \"piRNA clusters\" lack hallmarks of active genes and exploit an alternative path for transcription, which relies on the Rhino-Deadlock-Cutoff (RDC) complex. RDC was thought to be absent in testis, so it remains to date unknown how piRNA cluster transcription is regulated in the male germline. We found that components of RDC complex are expressed in male germ cells during early spermatogenesis, from germline stem cells (GSCs) to early spermatocytes. RDC is essential for expression of dual-strand piRNA clusters and transposon silencing in testis; however, it is dispensable for expression of Y-linked Suppressor of Stellate piRNAs and therefore Stellate silencing. Despite intact Stellate repression, males lacking RDC exhibited compromised fertility accompanied by germline DNA damage and GSC loss. Thus, piRNA-guided repression is essential for normal spermatogenesis beyond Stellate silencing. While RDC associates with multiple piRNA clusters in GSCs and early spermatogonia, its localization changes in later stages as RDC concentrates on a single X-linked locus, AT-chX. Dynamic RDC localization is paralleled by changes in piRNA cluster expression, indicating that RDC executes a fluid piRNA program during different stages of spermatogenesis. These results disprove the common belief that RDC is dispensable for piRNA biogenesis in testis and uncover the unexpected, sexually dimorphic and dynamic behavior of a core piRNA pathway machinery.", "date": "2021-09-02", "date_type": "published", "publication": "PLoS Genetics", "volume": "17", "number": "9", "publisher": "Public Library of Science", "pagerange": "Art. No. e1009591", "id_number": "CaltechAUTHORS:20200826-094353695", "issn": "1553-7390", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200826-094353695", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "R01 GM097363" } ] }, "local_group": { "items": [ { "id": "Millard-and-Muriel-Jacobs-Genetics-and-Genomics-Laboratory" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1371/journal.pgen.1009591", "pmcid": "PMC8412364", "primary_object": { "basename": "journal.pgen.1009591.s001.tif", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.s001.tif" }, "related_objects": [ { "basename": "journal.pgen.1009591.s002.tif", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.s002.tif" }, { "basename": "journal.pgen.1009591.s003.tif", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.s003.tif" }, { "basename": "journal.pgen.1009591.s004.tif", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.s004.tif" }, { "basename": "journal.pgen.1009591.s005.tif", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.s005.tif" }, { "basename": "2020.08.25.266643v1.full.pdf", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/2020.08.25.266643v1.full.pdf" }, { "basename": "journal.pgen.1009591.pdf", "url": "https://authors.library.caltech.edu/records/tcp03-tva18/files/journal.pgen.1009591.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Chen, Peiwei; Luo, Yicheng; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/t1kv0-v6v13", "eprint_id": 104390, "eprint_status": "archive", "datestamp": "2023-08-22 10:25:42", "lastmod": "2023-12-22 23:09:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Huang-Xiawei", "name": { "family": "Huang", "given": "Xiawei" }, "orcid": "0000-0001-9084-0510" }, { "id": "Hu-Hongmiao", "name": { "family": "Hu", "given": "Hongmiao" } }, { "id": "Webster-Alexandre", "name": { "family": "Webster", "given": "Alexandre" }, "orcid": "0000-0002-1416-5872" }, { "id": "Zou-Fan", "name": { "family": "Zou", "given": "Fan" } }, { "id": "Du-Jiamu", "name": { "family": "Du", "given": "Jiamu" } }, { "id": "Patel-Dinshaw-J", "name": { "family": "Patel", "given": "Dinshaw J." }, "orcid": "0000-0002-9779-7778" }, { "id": "Sachidanandam-Ravi", "name": { "family": "Sachidanandam", "given": "Ravi" }, "orcid": "0000-0001-9844-4459" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Li-Sisi", "name": { "family": "Li", "given": "Sisi" }, "orcid": "0000-0002-7290-8128" } ] }, "title": "Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex", "ispublished": "pub", "full_text_status": "public", "keywords": "Piwi RNAs; X-ray crystallography", "note": "\u00a9 The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 21 October 2020; Accepted 10 June 2021; Published 01 July 2021. \n\nWe thank members of the Aravin lab for their discussion and comments. We thank the BL19U1 beamlines staff at the Shanghai Synchrotron Radiation Facility for assistance during data collection. We thank Igor Antoshechkin (Caltech) for help with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to A.A.A. and the National Natural Science Foundation of China (31870755) and the Guangdong Innovation Research Team Fund (2016ZT06S172) to S.L. \n\nData availability: All relevant data supporting the key findings of this study are available within the article and its Supplementary Information files or from the corresponding authors upon reasonable request. The Drosophila strains that we have used in this report are also available from the corresponding authors upon reasonable request. Source data are provided with this paper. Small RNA-seq data are available on the GEO database, GSE153156. \n\nX-ray structures have been deposited in the RCSB Protein Data Bank with the accession codes: 7CFB for the eTud1 apo structure, 7CFC for the eTud1-Ago3 complex structure, and 7CFD for the eTud2-AubR15me2 structure. Source data are provided with this paper. \n\nThese authors contributed equally: Xiawei Huang, Hongmiao Hu. \n\nAuthor Contributions: S.L. and D.J.P. conceived and supervised ITC and structural work; A.A.A. conceived and supervised all other experiments. X.H., H.H., F.Z., and A.W. performed the experiments. R.S. developed tools for the analysis of small RNA libraries. A.A.A., X.H., H.H., K.F.T., and S.L. wrote the manuscript. \n\nThe authors declare no competing interests. \n\nPeer review information: Nature communications thanks Jinrong Min and other, anonymous, reviewers for their contributions to the peer review of this work. Peer review reports are available.\n\nPublished - s41467-021-24351-x.pdf
Submitted - 2020.07.14.203323v1.full.pdf
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Supplemental Material - 41467_2021_24351_MOESM3_ESM.pdf
Supplemental Material - 41467_2021_24351_MOESM4_ESM.xlsx
", "abstract": "PIWI proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two PIWI proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility. Methylation is triggered by loading of a piRNA guide into Aub, which exposes its unstructured N-terminal region to the PRMT5 methylosome complex. Thus, sDMA modification is a signal that Aub is loaded with piRNA guide. Amplification of piRNA in the ping-pong cycle requires assembly of a tertiary complex scaffolded by Krimper, which simultaneously binds the N-terminal regions of Aub and Ago3. To promote generation of new piRNA, Krimper uses its two Tudor domains to bind Aub and Ago3 in opposite modification and piRNA-loading states. Our results reveal that post-translational modifications in unstructured regions of PIWI proteins and their binding by Tudor domains that are capable of discriminating between modification states is essential for piRNA biogenesis and silencing.", "date": "2021-07-01", "date_type": "published", "publication": "Nature Communications", "volume": "12", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 4061", "id_number": "CaltechAUTHORS:20200715-143612345", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200715-143612345", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "National Natural Science Foundation of China", "grant_number": "31870755" }, { "agency": "Guangdong Innovation Research Team Fund", "grant_number": "2016ZT06S172" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41467-021-24351-x", "primary_object": { "basename": "2020.07.14.203323v1.full.pdf", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/2020.07.14.203323v1.full.pdf" }, "related_objects": [ { "basename": "41467_2021_24351_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/41467_2021_24351_MOESM1_ESM.pdf" }, { "basename": "41467_2021_24351_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/41467_2021_24351_MOESM2_ESM.pdf" }, { "basename": "41467_2021_24351_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/41467_2021_24351_MOESM3_ESM.pdf" }, { "basename": "41467_2021_24351_MOESM4_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/41467_2021_24351_MOESM4_ESM.xlsx" }, { "basename": "s41467-021-24351-x.pdf", "url": "https://authors.library.caltech.edu/records/t1kv0-v6v13/files/s41467-021-24351-x.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Huang, Xiawei; Hu, Hongmiao; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/yv03r-cqn98", "eprint_id": 110361, "eprint_status": "archive", "datestamp": "2023-08-20 04:01:52", "lastmod": "2023-12-22 23:23:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-Lidia", "name": { "family": "Lisitskaya", "given": "L." }, "orcid": "0000-0002-5283-7983" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "D." }, "orcid": "0000-0002-3706-4425" }, { "id": "Komar-Anna", "name": { "family": "Komar", "given": "A." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Analysis of a putative nuclease associated with the Argonaute protein from Rhodobacter sphaeroides", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021 The Authors. FEBS Open Bio \u00a9 2021 FEBS. \n\nIssue Online: 02 July 2021; Version of Record online: 02 July 2021. \n\nThis work was supported in part by the Russian Science Foundation (grant 191400359).\n\nPublished - Lisitskaya_2021_p238.pdf
", "abstract": "The Argonaute protein from the alphaproteobacterium Rhodobacter sphaeroides (RsAgo) binds small guide RNAs to recognize complementary DNA targets. In bacterial cells, RsAgo is bound to both small RNAs and small DNAs, with a preference for foreign genetic elements. RsAgo also promotes degradation of plasmid DNA in vivo. However, RsAgo itself lacks the slicer activity, suggesting the involvement of additional nucleases. To shed light on the molecular mechanism of target processing, we study a putative nuclease which is located in the same operon with RsAgo in the R. sphaeroides genome. This protein has motifs characteristic for the PD(D/E)XK superfamily of nucleases. Numerous attempts to express the wildtype nuclease gene in Escherichia coli were not successful due to a low level of expression and low solubility of the recombinant protein. A codon-optimized sequence of the nuclease gene was cloned and sucessfully overexpressed in E. coli. Different expression vectors were used to produce histidine-tagged nuclease and a fusion protein with a chitin-binding domain, which allowed to obtain highly pure nuclease preparations. Initial assays did not reveal nuclease activity in these proteins. However, it was shown that coexpression of nuclease with the RsAgo protein in E. coli significantly increases the yield of RsAgo and changes the spectrum of genes preferentially targeted by RsAgo. We plan to further determine the role of nuclease in DNA processing in bacterial cells and test its interactions with RsAgo in vitro and in vivo.", "date": "2021-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "11", "number": "S1", "publisher": "Wiley", "pagerange": "238", "id_number": "CaltechAUTHORS:20210821-161228936", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210821-161228936", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "191400359" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1002/2211-5463.13205", "primary_object": { "basename": "Lisitskaya_2021_p238.pdf", "url": "https://authors.library.caltech.edu/records/yv03r-cqn98/files/Lisitskaya_2021_p238.pdf" }, "resource_type": "article", "pub_year": "2021", "author_list": "Lisitskaya, L.; Esyunina, D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xfg71-pcp50", "eprint_id": 105115, "eprint_status": "archive", "datestamp": "2023-08-22 09:57:40", "lastmod": "2023-12-22 23:41:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Peiwei", "name": { "family": "Chen", "given": "Peiwei" }, "orcid": "0000-0001-7160-6673" }, { "id": "Kotov-Alexei-A", "name": { "family": "Kotov", "given": "Alexei A." }, "orcid": "0000-0002-5866-3574" }, { "id": "Godneeva-Baira-K", "name": { "family": "Godneeva", "given": "Baira K." } }, { "id": "Bazylev-Sergei-S", "name": { "family": "Bazylev", "given": "Sergei S." } }, { "id": "Olenina-Ludmila-V", "name": { "family": "Olenina", "given": "Ludmila V." }, "orcid": "0000-0002-7422-4387" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "piRNA-mediated gene regulation and adaptation to sex-specific transposon expression in D. melanogaster male germline", "ispublished": "pub", "full_text_status": "public", "keywords": "Drosophila mauritiana; Drosophila melanogaster; Y chromosome; piRNA; satellite DNA; sexual dimorphism; spermatogenesis; transposable element", "note": "\u00a9 2021 Chen et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. \n\nReceived September 21, 2020. Accepted April 8, 2021. Published in Advance May 13, 2021. \n\nData availability: Sequencing data can be accessed via NCBI SRA with the following accession numbers: PRJNA646006 (rhi), PRJNA646216 (aub, zuc, and spn-E), and PRJNA719671 (degradome). \n\nWe are grateful to William Theurkauf, Trudi Sch\u00fcpbach, Julius Brennecke, and the Bloomington Drosophila Stock Center for fly stocks.We thank Katalin Fejes Toth and members of the Aravin laboratory for discussion, and Silke Jensen and Emilie Brasset for valuable comments on the preprint. We appreciate the help of Maria Ninova and Fan Gao (Bioinformatics Resource Center, California Institute of Technology) with bioinformatics analysis, the help of Pei-Hsuan Wu and Ildar Gainetdinov (Phil Zamore's laboratory) with degradome-seq experiments, the help of Grace Shin and Maayan Schwarzkopf with HCR experiments, the help of Giada Spigolon and Andres Collazo (Biological Imaging Facility, California Institute of Technology) with microscopy, and the help of Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, California Institute of Technology) with sequencing. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the Howard Hughes Medical Institute Faculty Scholar Award to A.A.A. \n\nAuthor contributions: P.C. conducted most experiments and most bioinformatic analysis. B.K.G. performed testis RNA-seq. All authors designed experiments and analyzed the data. P.C. and A.A.A. wrote the manuscript with input from all other coauthors. \n\nThe authors declare no competing interests.\n\nPublished - Genes_Dev.-2021-Chen-914-35.pdf
Submitted - 2020.08.25.266585v1.full.pdf
Supplemental Material - Supplementary_Figures.pdf
Supplemental Material - Supplementary_Table_S1.xlsx
", "abstract": "Small noncoding piRNAs act as sequence-specific guides to repress complementary targets in Metazoa. Prior studies in Drosophila ovaries have demonstrated the function of the piRNA pathway in transposon silencing and therefore genome defense. However, the ability of the piRNA program to respond to different transposon landscapes and the role of piRNAs in regulating host gene expression remain poorly understood. Here, we comprehensively analyzed piRNA expression and defined the repertoire of their targets in Drosophila melanogaster testes. Comparison of piRNA programs between sexes revealed sexual dimorphism in piRNA programs that parallel sex-specific transposon expression. Using a novel bioinformatic pipeline, we identified new piRNA clusters and established complex satellites as dual-strand piRNA clusters. While sharing most piRNA clusters, the two sexes employ them differentially to combat the sex-specific transposon landscape. We found two piRNA clusters that produce piRNAs antisense to four host genes in testis, including CG12717/pirate, a SUMO protease gene. piRNAs encoded on the Y chromosome silence pirate, but not its paralog, to exert sex- and paralog-specific gene regulation. Interestingly, pirate is targeted by endogenous siRNAs in a sibling species, Drosophila mauritiana, suggesting distinct but related silencing strategies invented in recent evolution to regulate a conserved protein-coding gene.", "date": "2021-06", "date_type": "published", "publication": "Genes and Development", "volume": "35", "number": "11-12", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "914-935", "id_number": "CaltechAUTHORS:20200826-100150960", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200826-100150960", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Millard-and-Muriel-Jacobs-Genetics-and-Genomics-Laboratory" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/gad.345041.120", "pmcid": "PMC8168559", "primary_object": { "basename": "2020.08.25.266585v1.full.pdf", "url": "https://authors.library.caltech.edu/records/xfg71-pcp50/files/2020.08.25.266585v1.full.pdf" }, "related_objects": [ { "basename": "Genes_Dev.-2021-Chen-914-35.pdf", "url": "https://authors.library.caltech.edu/records/xfg71-pcp50/files/Genes_Dev.-2021-Chen-914-35.pdf" }, { "basename": "Supplementary_Figures.pdf", "url": "https://authors.library.caltech.edu/records/xfg71-pcp50/files/Supplementary_Figures.pdf" }, { "basename": "Supplementary_Table_S1.xlsx", "url": "https://authors.library.caltech.edu/records/xfg71-pcp50/files/Supplementary_Table_S1.xlsx" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Chen, Peiwei; Kotov, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fd60q-k4226", "eprint_id": 107892, "eprint_status": "archive", "datestamp": "2023-08-20 02:46:35", "lastmod": "2023-12-22 23:13:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kropocheva-Ekaterina", "name": { "family": "Kropocheva", "given": "Ekaterina" }, "orcid": "0000-0001-8895-0577" }, { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Kulbachiskiy-Andrey", "name": { "family": "Kulbachiskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "A programmable pAgo nuclease with universal guide and target specificity from the mesophilic bacterium Kurthia massiliensis", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived February 04, 2021; Revised March 02, 2021; Editorial Decision March 03, 2021; Accepted March 06, 2021; Published: 21 March 2021. \n\nWe thank Sergei Ryazansky for help with bioinformatic analysis of pAgo proteins and Denis Yudin for initial analysis of smDNA libraries. \n\nFunding: Russian Foundation for Basic Research [18-29-07086 to A.K.; biochemical analysis of KmAgo]; Russian Science Foundation [19-14-00359 to D.E.; analysis of in vivo activities of KmAgo]. Funding for open access charge: Russian Foundation for Basic Research. \n\nData Availability: The smDNA sequencing datasets generated in this study are available from the Gene Expression Omnibus (GEO) database under the accession number GSE168010. \n\nConflict of interest statement. None declared.\n\nPublished - gkab182.pdf
Submitted - 2021.02.03.429301v1.full.pdf
Supplemental Material - gkab182_supplemental_file.pdf
", "abstract": "Argonaute proteins are programmable nucleases that are found in both eukaryotes and prokaryotes and provide defense against invading genetic elements. Although some prokaryotic argonautes (pAgos) were shown to recognize RNA targets in vitro, the majority of studied pAgos have strict specificity toward DNA, which limits their practical use in RNA-centric applications. Here, we describe a unique pAgo nuclease, KmAgo, from the mesophilic bacterium Kurthia massiliensis that can be programmed with either DNA or RNA guides and can precisely cleave both DNA and RNA targets. KmAgo binds 16\u201320 nt long 5\u2032-phosphorylated guide molecules with no strict specificity for their sequence and is active in a wide range of temperatures. In bacterial cells, KmAgo is loaded with small DNAs with no obvious sequence preferences suggesting that it can uniformly target genomic sequences. Mismatches between the guide and target sequences greatly affect the efficiency and precision of target cleavage, depending on the mismatch position and the nature of the reacting nucleic acids. Target RNA cleavage by KmAgo depends on the formation of secondary structure indicating that KmAgo can be used for structural probing of RNA. These properties of KmAgo open the way for its use for highly specific nucleic acid detection and cleavage.", "date": "2021-04-19", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "49", "number": "7", "publisher": "Oxford University Press", "pagerange": "4054-4065", "id_number": "CaltechAUTHORS:20210203-143505325", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210203-143505325", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "18-29-07086" }, { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1093/nar/gkab182", "pmcid": "PMC8053121", "primary_object": { "basename": "2021.02.03.429301v1.full.pdf", "url": "https://authors.library.caltech.edu/records/fd60q-k4226/files/2021.02.03.429301v1.full.pdf" }, "related_objects": [ { "basename": "gkab182.pdf", "url": "https://authors.library.caltech.edu/records/fd60q-k4226/files/gkab182.pdf" }, { "basename": "gkab182_supplemental_file.pdf", "url": "https://authors.library.caltech.edu/records/fd60q-k4226/files/gkab182_supplemental_file.pdf" } ], "resource_type": "article", "pub_year": "2021", "author_list": "Kropocheva, Ekaterina; Kuzmenko, Anton; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/6xp4k-42a66", "eprint_id": 108124, "eprint_status": "archive", "datestamp": "2023-08-20 01:29:37", "lastmod": "2023-12-22 23:12:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Adashev-Vladimir-E", "name": { "family": "Adashev", "given": "Vladimir E." } }, { "id": "Kotov-Alexei-A", "name": { "family": "Kotov", "given": "Alexei A." }, "orcid": "0000-0002-5866-3574" }, { "id": "Bazylev-Sergei-S", "name": { "family": "Bazylev", "given": "Sergei S." } }, { "id": "Shatskikh-Aleksei-S", "name": { "family": "Shatskikh", "given": "Aleksei S." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Olenina-Ludmila-V", "name": { "family": "Olenina", "given": "Ludmila V." }, "orcid": "0000-0002-7422-4387" } ] }, "title": "Stellate Genes and the piRNA Pathway in Speciation and Reproductive Isolation of Drosophila melanogaster", "ispublished": "pub", "full_text_status": "public", "keywords": "Drosophila, Stellate genes, piRNA pathway, reproductive isolation, hybrid sterility", "note": "\u00a9 2021 Adashev, Kotov, Bazylev, Shatskikh, Aravin and Olenina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. \n\nReceived: 26 September 2020; Accepted: 29 December 2020; Published: 22 January 2021. \n\nWe thank A. D. Stolyarenko for discussions on this manuscript. \n\nThis work was funded by RFBR, project number #20-04-00562. \n\nAuthor Contributions. VA and LO prepared the initial version of the manuscript and created the figures. AK, SB, AS, and AA rigorously revised and improved the manuscript. VA, LO, AK, and AA polished the final version of the manuscript. All authors provided intellectual contribution, edited, and approved the manuscript for publication in its present version. \n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nPublished - fgene-11-610665.pdf
", "abstract": "One of the main conditions of the species splitting from a common precursor lineage is the prevention of a gene flow between diverging populations. The study of Drosophila interspecific hybrids allows to reconstruct the speciation mechanisms and to identify hybrid incompatibility factors that maintain post-zygotic reproductive isolation between closely related species. The regulation, evolution, and maintenance of the testis-specific Ste-Su(Ste) genetic system in Drosophila melanogaster is the subject of investigation worldwide. X-linked tandem testis-specific Stellate genes encode proteins homologous to the regulatory \u03b2-subunit of protein kinase CK2, but they are permanently repressed in wild-type flies by the piRNA pathway via piRNAs originating from the homologous Y-linked Su(Ste) locus. Derepression of Stellate genes caused by Su(Ste) piRNA biogenesis disruption leads to the accumulation of crystalline aggregates in spermatocytes, meiotic defects and male sterility. In this review we summarize current data about the origin, organization, evolution of the Ste-Su(Ste) system, and piRNA-dependent regulation of Stellate expression. The Ste-Su(Ste) system is fixed only in the D. melanogaster genome. According to our hypothesis, the acquisition of the Ste-Su(Ste) system by a part of the ancient fly population appears to be the causative factor of hybrid sterility in crosses of female flies with males that do not carry Y-linked Su(Ste) repeats. To support this scenario, we have directly demonstrated Stellate derepression and the corresponding meiotic disorders in the testes of interspecies hybrids between D. melanogaster and D. mauritiana. This finding embraces our hypothesis about the contribution of the Ste-Su(Ste) system and the piRNA pathway to the emergence of reproductive isolation of D. melanogaster lineage from initial species.", "date": "2021-01-22", "date_type": "published", "publication": "Frontiers in Genetics", "volume": "11", "publisher": "Frontiers Research Foundation", "pagerange": "Art. No. 610665", "id_number": "CaltechAUTHORS:20210219-120046711", "issn": "1664-8021", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210219-120046711", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "20-04-00562" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.3389/fgene.2020.610665", "pmcid": "PMC7874207", "primary_object": { "basename": "fgene-11-610665.pdf", "url": "https://authors.library.caltech.edu/records/6xp4k-42a66/files/fgene-11-610665.pdf" }, "resource_type": "article", "pub_year": "2021", "author_list": "Adashev, Vladimir E.; Kotov, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/14fvt-q2608", "eprint_id": 106294, "eprint_status": "archive", "datestamp": "2023-08-22 08:03:15", "lastmod": "2023-12-22 23:13:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-Lidia", "name": { "family": "Lisitskaya", "given": "Lidia" }, "orcid": "0000-0002-5283-7983" }, { "id": "Petushkov-Ivan", "name": { "family": "Petushkov", "given": "Ivan" } }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Recognition of double-stranded DNA by the Rhodobacter sphaeroides Argonaute protein", "ispublished": "pub", "full_text_status": "public", "keywords": "Argonaute proteins; pAgo; Small RNA; Small DNA; DNA targeting", "note": "\u00a9 2020 Elsevier Inc. \n\nReceived 15 October 2020, Accepted 18 October 2020, Available online 24 October 2020. \n\nThis work was supported in part by the Russian Science Foundation (19-14-00359; analysis of ternary complex formation) and the Russian Foundation for Basic Research (18-29-07086; footprinting experiments). \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nSupplemental Material - 1-s2.0-S0006291X20319690-mmc1.pdf
", "abstract": "In contrast to eukaryotic Argonaute proteins that act on RNA targets, prokaryotic Argonautes (pAgos) can target DNA, using either small RNA or small DNA guides for its recognition. Since pAgos can recognize only a single strand of DNA and lack a helicase activity, it remains unknown how double-stranded DNA can be bound both in vitro and in vivo. Here, using in vitro reconstitution and footprinting assays we analyze formation of specific complexes with target DNA by a catalytically inactive pAgo, RsAgo from Rhodobacter sphaeroides programmed with small guide RNAs. We showed that RsAgo can recognize a specific site in double-stranded DNA after stepwise reconstitution of the complex from individual oligonucleotides or after prior melting of the DNA target. When bound, RsAgo stabilizes an open DNA bubble corresponding to the length of the guide molecule and protects the target DNA from nuclease cleavage. The results suggest that RsAgo and, possibly, other RNA-guided pAgos cannot directly attack double-stranded DNA and likely require DNA opening by other cellular processes for their action.", "date": "2020-12-17", "date_type": "published", "publication": "Biochemical and Biophysical Research Communications", "volume": "533", "number": "4", "publisher": "Elsevier", "pagerange": "1484-1489", "id_number": "CaltechAUTHORS:20201027-090926979", "issn": "0006-291X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201027-090926979", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "18-29-07086" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.bbrc.2020.10.051", "primary_object": { "basename": "1-s2.0-S0006291X20319690-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/14fvt-q2608/files/1-s2.0-S0006291X20319690-mmc1.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Lisitskaya, Lidia; Petushkov, Ivan; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ezgvq-4pc09", "eprint_id": 101694, "eprint_status": "archive", "datestamp": "2023-08-22 07:42:24", "lastmod": "2023-12-22 23:23:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Oguienko-Anastasiya", "name": { "family": "Oguienko", "given": "Anastasiya" }, "orcid": "0000-0002-8473-6378" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Yudin-Denis", "name": { "family": "Yudin", "given": "Denis" }, "orcid": "0000-0002-4103-0543" }, { "id": "Petrova-Mayya", "name": { "family": "Petrova", "given": "Mayya" }, "orcid": "0000-0001-5411-0457" }, { "id": "Kudinova-Alina", "name": { "family": "Kudinova", "given": "Alina" } }, { "id": "Maslova-Olga", "name": { "family": "Maslova", "given": "Olga" } }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Ryazansky-Sergei", "name": { "family": "Ryazansky", "given": "Sergei" }, "orcid": "0000-0002-3171-2997" }, { "id": "Leach-David", "name": { "family": "Leach", "given": "David" }, "orcid": "0000-0003-4964-6913" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "DNA targeting and interference by a bacterial Argonaute nuclease", "ispublished": "pub", "full_text_status": "public", "keywords": "Bacterial host response; Phage biology; RNAi", "note": "\u00a9 2020 Nature Publishing Group. \n\nReceived 05 March 2020; Accepted 24 July 2020; Published 30 July 2020. \n\nWe thank M. A. White for strains with engineered I-SceI sites, G. Smith for RecBCD antibodies, S. Lysenkov for the help with statistical analysis and A. Olina for the help with the phage experiments. D.Y. would like to thank M. Kolesnik for discussions. The project was in part supported by the Ministry of Science and Higher Education of the Russian Federation (14.W03.31.0007), Russian Science Foundation (19-14-00359, analysis of DSB formation), Russian Foundation for Basic Research (18-29-07086). A.A.A. is supported by an HHMI Faculty Scholar Award. D.L. is supported by grant MR/M019160/1 from the MRC (UK). \n\nData availability: All data generated during this study are included in the published Article and the Extended Data and are available from the Gene Expression Omnibus (GEO) database with the accession number GSE148596. \n\nCode availability: The code used for data analysis is available at the GitHub repository at https://github.com/AntKuzmenko/CbAgo_DNAi.git. \n\nAuthor Contributions: A. Kuzmenko, A.A.A. and A. Kulbachinskiy conceptualized the study. A. Kuzmenko, D.Y. and D.E. constructed strains. A. Kuzmenko, A.O., D.Y. and D.E. prepared smDNA libraries. A. Kuzmenko, A.O. and D.E. prepared genomic DNA libraries. A. Kuzmenko, A.O. and D.Y. analysed sequencing data, M.N. and S.R. helped with data analysis. S.R. performed phylogenetic analysis. D.L. conceptualized experiments with engineered DSBs. A. Kuzmenko, A. Kudinova, O.M., M.P., A.O. and D.E. performed experiments on plasmid elimination and phage infection. All authors interpreted the results. A. Kuzmenko and A.O. prepared the figures. A. Kulbachinskiy and A.A.A. wrote the manuscript with contribution from other authors. \n\nThe authors declare no competing interests.\n\nSubmitted - 2020.03.01.971358v1.full.pdf
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", "abstract": "Members of the conserved Argonaute protein family use small RNA guides to locate their mRNA targets and regulate gene expression and suppress mobile genetic elements in eukaryotes. Argonautes are also present in many bacterial and archaeal species. Unlike eukaryotic proteins, several prokaryotic Argonaute proteins use small DNA guides to cleave DNA, a process known as DNA interference. However, the natural functions and targets of DNA interference are poorly understood, and the mechanisms of DNA guide generation and target discrimination remain unknown. Here we analyse the activity of a bacterial Argonaute nuclease from Clostridium butyricum (CbAgo) in vivo. We show that CbAgo targets multicopy genetic elements and suppresses the propagation of plasmids and infection by phages. CbAgo induces DNA interference between homologous sequences and triggers DNA degradation at double-strand breaks in the target DNA. The loading of CbAgo with locus-specific small DNA guides depends on both its intrinsic endonuclease activity and the cellular double-strand break repair machinery. A similar interaction was reported for the acquisition of new spacers during CRISPR adaptation, and prokaryotic genomes that encode Ago nucleases are enriched in CRISPR\u2013Cas systems. These results identify molecular mechanisms that generate guides for DNA interference and suggest that the recognition of foreign nucleic acids by prokaryotic defence systems involves common principles.", "date": "2020-11-26", "date_type": "published", "publication": "Nature", "volume": "587", "number": "7835", "publisher": "Nature Publishing Group", "pagerange": "632-637", "id_number": "CaltechAUTHORS:20200304-081912707", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200304-081912707", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "Russian Science Foundation", "grant_number": "19-14-00359" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "18-29-07086" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Medical Research Council (UK)", "grant_number": "MR/M019160/1" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41586-020-2605-1", "primary_object": { "basename": "41586_2020_2605_Fig14_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig14_ESM.webp" }, "related_objects": [ { "basename": "41586_2020_2605_Fig6_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig6_ESM.webp" }, { "basename": "41586_2020_2605_Fig8_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig8_ESM.webp" }, { "basename": "41586_2020_2605_Fig7_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig7_ESM.webp" }, { "basename": "41586_2020_2605_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_MOESM1_ESM.pdf" }, { "basename": "41586_2020_2605_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_MOESM2_ESM.pdf" }, { "basename": "41586_2020_2605_Fig11_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig11_ESM.webp" }, { "basename": "41586_2020_2605_Fig13_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig13_ESM.webp" }, { "basename": "41586_2020_2605_Fig5_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig5_ESM.webp" }, { "basename": "41586_2020_2605_MOESM4_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_MOESM4_ESM.pdf" }, { "basename": "2020.03.01.971358v1.full.pdf", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/2020.03.01.971358v1.full.pdf" }, { "basename": "41586_2020_2605_Fig10_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig10_ESM.webp" }, { "basename": "41586_2020_2605_Fig12_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig12_ESM.webp" }, { "basename": "41586_2020_2605_Fig9_ESM.webp", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_Fig9_ESM.webp" }, { "basename": "41586_2020_2605_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ezgvq-4pc09/files/41586_2020_2605_MOESM3_ESM.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Kuzmenko, Anton; Oguienko, Anastasiya; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bm3nd-efb29", "eprint_id": 104392, "eprint_status": "archive", "datestamp": "2023-08-20 00:19:25", "lastmod": "2023-12-22 23:13:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Fefelova-Elena", "name": { "family": "Fefelova", "given": "Elena" } }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Repression of interrupted and intact rDNA by the SUMO pathway in Drosophila melanogaster", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2020 Luo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived: 03 October 2019; Accepted: 06 November 2020; Published: 09 November 2020. \n\nWe thank Katalin Fejes Toth and members of the Aravin lab for discussion and comments. We appreciate the help of Maayan Schwarzkopf and Niles Pierce with HCR-FISH experiments. We thank Lynn Yi for help with bioinformatics analysis. We are grateful to Michael Buszczak and the Bloomington Stock Center for providing fly stocks, Igor Dawid for providing rDNA unit constructs. We thank Igor Antoshechkin (Caltech) for help with sequencing. MN is supported by NIH/NICHD grant (K99HD099316). This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to AAA. \n\nTThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nAuthor contributions:\nYicheng Luo, Formal analysis, Investigation, Visualization, Writing - original draft; Elena Fefelova, Formal analysis, Investigation, Writing - original draft; Maria Ninova, Software, Formal analysis, Visualization; Yung-Chia Ariel Chen, Investigation; Alexei A Aravin, Conceptualization, Supervision, Funding acquisition, Validation, Methodology, Writing - original draft, Project administration, Writing - review and editing. \n\nData availability: Sequencing data have been deposited in GEO under accession codes GSE141068 and GSE115277.\nOther data generated or analysed during this study are included in the manuscript and supporting files. \n\nThe following datasets were generated: \n\nLuo Y, Fefelova E, Ninova M, Chen YA, Aravin AA. 2020. Repression of damaged and intact rDNA by the SUMO pathway. NCBI Gene Expression Omnibus. GSE141068 \n\nNinova M, Chen YA, Godneeva B, Rogers A, Luo Y, T\u00f3th KF, Aravin AA. 2019. The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing. NCBI Gene Expression Omnibus. GSE115277 \n\nThe following previously published dataset was used: \n\nGonzalez I, Mateos-Langerak J, Thomas A, Cheutin T, Cavalli G. 2014. Identification of Regulators of the Three-Dimensional Polycomb Organization by a Microscopy-Based Genome-Wide RNAi Screen. NCBI Gene Expression Omnibus. GSE55303\n\nPublished - elife-52416-v2.pdf
Submitted - 2020.07.14.203158v1.full.pdf
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", "abstract": "Ribosomal RNAs (rRNAs) are essential components of the ribosome and are among the most abundant macromolecules in the cell. To ensure high rRNA level, eukaryotic genomes contain dozens to hundreds of rDNA genes, however, only a fraction of the rRNA genes seems to be active, while others are transcriptionally silent. We found that individual rDNA genes have high level of cell-to-cell heterogeneity in their expression in Drosophila melanogaster. Insertion of heterologous sequences into rDNA leads to repression associated with reduced expression in individual cells and decreased number of cells expressing rDNA with insertions. We found that SUMO (Small Ubiquitin-like Modifier) and SUMO ligase Ubc9 are required for efficient repression of interrupted rDNA units and variable expression of intact rDNA. Disruption of the SUMO pathway abolishes discrimination of interrupted and intact rDNAs and removes cell-to-cell heterogeneity leading to uniformly high expression of individual rDNA in single cells. Our results suggest that the SUMO pathway is responsible for both repression of interrupted units and control of intact rDNA expression.", "date": "2020-11-09", "date_type": "published", "publication": "eLife", "volume": "2020", "number": "9", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e52416", "id_number": "CaltechAUTHORS:20200715-153524216", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200715-153524216", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99HD099316" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/eLife.52416", "pmcid": "PMC7676866", "primary_object": { "basename": "2020.07.14.203158v1.full.pdf", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/2020.07.14.203158v1.full.pdf" }, "related_objects": [ { "basename": "elife-52416-supp-v1.zip", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp-v1.zip" }, { "basename": "elife-52416-supp2-v2.docx", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp2-v2.docx" }, { "basename": "elife-52416-supp3-v2.xlsx", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp3-v2.xlsx" }, { "basename": "elife-52416-supp4-v2.docx", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp4-v2.docx" }, { "basename": "elife-52416-supp1-v2.docx", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp1-v2.docx" }, { "basename": "elife-52416-supp5-v2.xlsx", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-supp5-v2.xlsx" }, { "basename": "elife-52416-transrepform-v2.pdf", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-transrepform-v2.pdf" }, { "basename": "elife-52416-v2.pdf", "url": "https://authors.library.caltech.edu/records/bm3nd-efb29/files/elife-52416-v2.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Luo, Yicheng; Fefelova, Elena; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/btg15-m0t58", "eprint_id": 104133, "eprint_status": "archive", "datestamp": "2023-08-19 22:05:48", "lastmod": "2023-12-22 23:13:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Pachytene piRNAs as beneficial regulators or a defense system gone rogue", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2020 Springer Nature Limited. \n\nPublished 29 June 2020. \n\nThe author declares no competing interests.", "abstract": "Pachytene Piwi-interacting RNAs (piRNAs) are abundant small non-coding RNAs expressed in mammalian germ lines. A new study indicates that, among the diverse pool of piRNA sequences, a small number act as highly selective guides that induce cleavage of coding and non-coding transcripts, thus promoting piRNA generation and regulating gene expression.", "date": "2020-07", "date_type": "published", "publication": "Nature Genetics", "volume": "52", "number": "7", "publisher": "Nature Publishing Group", "pagerange": "644-645", "id_number": "CaltechAUTHORS:20200629-132840404", "issn": "1061-4036", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200629-132840404", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41588-020-0656-8", "resource_type": "article", "pub_year": "2020", "author_list": "Aravin, Alexei A." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/by7hj-q9q39", "eprint_id": 101249, "eprint_status": "archive", "datestamp": "2023-08-19 19:59:41", "lastmod": "2023-12-22 23:23:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olina-Anna", "name": { "family": "Olina", "given": "Anna" }, "orcid": "0000-0003-1844-2109" }, { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" } ] }, "title": "Genome-wide DNA sampling by Ago nuclease from the cyanobacterium Synechococcus elongatus", "ispublished": "pub", "full_text_status": "public", "keywords": "Argonaute, programmable DNA nuclease, SeAgo, Synechococcus elongatus, ori and ter sites", "note": "\u00a9 2020 Informa UK Limited. \n\nReceived 15 Aug 2019, Accepted 12 Jan 2020, Accepted author version posted online: 03 Feb 2020, Published online: 16 Feb 2020.\n\nWe thank Denis Yudin for helpful discussions.\n\nThis work was supported by the Russian Science Foundation [16-14-10377]; Russian Foundation for Basic Research [18-29-07086].\n\nNo potential conflicts of interest were disclosed.\n\nSupplemental Material - krnb_a_1724716_sm9702.pdf
", "abstract": "Members of the conserved Argonaute (Ago) protein family provide defense against invading nucleic acids in eukaryotes in the process of RNA interference. Many prokaryotes also contain Ago proteins that are predicted to be active nucleases, however, their functional activities in host cells remain poorly understood. Here, we characterize the in vitro and in vivo properties of the SeAgo protein from the mesophilic cyanobacterium Synechococcus elongatus. We show that SeAgo is a DNA-guided nuclease preferentially acting on single-stranded DNA targets, with nonspecific guide-independent activity observed for double-stranded substrates. The SeAgo gene is steadily expressed in S. elongatus, however, its deletion or overexpression does not change the kinetics of cell growth. When purified from its host cells or from heterologous E. coli, SeAgo is loaded with small guide DNAs whose formation depends on the endonuclease activity of the argonaute protein. SeAgo co-purifies with SSB proteins suggesting that they may also be involved in DNA processing. The SeAgo-associated small DNAs are derived from diverse genomic locations, with certain enrichment for the proposed sites of chromosomal replication initiation and termination, but show no preference for an endogenous plasmid. Therefore, promiscuous genome sampling by SeAgo does not have great effects on cell physiology and plasmid maintenance.", "date": "2020-02-16", "date_type": "published", "publication": "RNA Biology", "volume": "17", "number": "5", "publisher": "Informa UK Limited", "pagerange": "677-688", "id_number": "CaltechAUTHORS:20200212-142110986", "issn": "1547-6286", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200212-142110986", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "16-14-10377" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "18-29-07086" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1080/15476286.2020.1724716", "pmcid": "PMC7237159", "primary_object": { "basename": "krnb_a_1724716_sm9702.pdf", "url": "https://authors.library.caltech.edu/records/by7hj-q9q39/files/krnb_a_1724716_sm9702.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Olina, Anna; Kuzmenko, Anton; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3zwcn-rwy84", "eprint_id": 92533, "eprint_status": "archive", "datestamp": "2023-08-22 03:59:45", "lastmod": "2023-12-22 23:08:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Godneeva-Baira-K", "name": { "family": "Godneeva", "given": "Baira" } }, { "id": "Rogers-A-K", "name": { "family": "Rogers", "given": "Alicia K." }, "orcid": "0000-0001-5525-6095" }, { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing", "ispublished": "pub", "full_text_status": "public", "keywords": "piRNA; Su(var)2-10; SUMO; chromatin; heterochromatin; silencing; transposon", "note": "\u00a9 2019 Elsevier Inc. \n\nReceived 13 February 2019, Revised 11 June 2019, Accepted 8 November 2019, Available online 31 December 2019. \n\nWe thank members of the Fejes Toth and Aravin labs for discussion. We thank Gary Karpen for suggestions and discussion of some of the experiments. We appreciate the help of Kathy Situ, Zs\u00f3fia T\u00f6r\u00f6k, Sivani Vempati, Solomiia Khomandiak, and Angel Galvez Merchan with the experiments. We are grateful to Julius Brennecke, Gregory Hannon, and the Bloomington Stock Center for providing fly stocks; Giacomo Cavalli for providing antibodies; Andreas Wodarz for the GFP-wde expression vector; and Guntram Suske for the GST-Smt3 (wild-type) plasmid. We thank Igor Antoshechkin (Caltech) for help with sequencing and Sergei Manakov for bioinformatic support. This work was supported by grants from the NIH (R01 GM097363) and the Ministry of Education and Science of Russian Federation (14.W03.31.0007) and by the Packard Fellowship Awards to A.A.A., and the NIH (R01GM110217) and the Ellison Medical Foundation Awards to K.F.T. A.K.R. was an NSF GRFP fellow. \n\nAuthor Contributions: M.N., Y.A.C., A.A.A., and K.F.T. designed the experiments. M.N., Y.A.C., B.G., A.R., K.F.T., and Y.L. executed the experiments. M.N. performed the computational analysis and interpretation of the data. The manuscript was written by M.N., Y.A.C., A.A.A., and K.F.T. \n\nThe authors declare no competing interests.\n\nAccepted Version - nihms-1544123.pdf
Submitted - 533091.1.full.pdf
Supplemental Material - 1-s2.0-S109727651930841X-mmc1.pdf
", "abstract": "Regulation of transcription is the main mechanism responsible for precise control of gene expression. Whereas the majority of transcriptional regulation is mediated by DNA-binding transcription factors that bind to regulatory gene regions, an elegant alternative strategy employs small RNA guides, Piwi-interacting RNAs (piRNAs) to identify targets of transcriptional repression. Here, we show that in Drosophila the small ubiquitin-like protein SUMO and the SUMO E3 ligase Su(var)2-10 are required for piRNA-guided deposition of repressive chromatin marks and transcriptional silencing of piRNA targets. Su(var)2-10 links the piRNA-guided target recognition complex to the silencing effector by binding the piRNA/Piwi complex and inducing SUMO-dependent recruitment of the SetDB1/Wde histone methyltransferase effector. We propose that in Drosophila, the nuclear piRNA pathway has co-opted a conserved mechanism of SUMO-dependent recruitment of the SetDB1/Wde chromatin modifier to confer repression of genomic parasites.", "date": "2020-02-06", "date_type": "published", "publication": "Molecular Cell", "volume": "77", "number": "3", "publisher": "Cell Press", "pagerange": "556-570", "id_number": "CaltechAUTHORS:20190130-162009709", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190130-162009709", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "NIH", "grant_number": "R01 GM110217" }, { "agency": "Ellison Medical Foundation" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.molcel.2019.11.012", "pmcid": "PMC7007863", "primary_object": { "basename": "1-s2.0-S109727651930841X-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/3zwcn-rwy84/files/1-s2.0-S109727651930841X-mmc1.pdf" }, "related_objects": [ { "basename": "533091.1.full.pdf", "url": "https://authors.library.caltech.edu/records/3zwcn-rwy84/files/533091.1.full.pdf" }, { "basename": "nihms-1544123.pdf", "url": "https://authors.library.caltech.edu/records/3zwcn-rwy84/files/nihms-1544123.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Ninova, Maria; Chen, Yung-Chia Ariel; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2st3h-t7d91", "eprint_id": 92523, "eprint_status": "archive", "datestamp": "2023-08-22 03:59:29", "lastmod": "2023-12-22 23:08:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Godneeva-Baira-K", "name": { "family": "Godneeva", "given": "Baira" } }, { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Prakash-Sharan-J", "name": { "family": "Prakash", "given": "Sharan J." }, "orcid": "0000-0003-1777-0987" }, { "id": "Jankovics-Ferec", "name": { "family": "Jankovics", "given": "Ferenc" }, "orcid": "0000-0001-9697-4472" }, { "id": "Erd\u00e9lyi-Mikl\u00f3s", "name": { "family": "Erd\u00e9lyi", "given": "Mikl\u00f3s" }, "orcid": "0000-0002-9501-5752" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" } ] }, "title": "The SUMO Ligase Su(var)2-10 Controls Hetero- and Euchromatic Gene Expression via Establishing H3K9 Trimethylation and Negative Feedback Regulation", "ispublished": "pub", "full_text_status": "public", "keywords": "chromatin; heterochromatin; epigenetics; gene regulation; transcriptional repression; transposons; germline; cell fate maintenance; SUMO; H3K9me3", "note": "\u00a9 2019 Elsevier Inc. \n\nReceived 13 February 2019, Revised 11 June 2019, Accepted 26 September 2019, Available online 31 December 2019. \n\nWe thank members of the Fejes T\u00f3th and Aravin labs for discussion. We are grateful to the Bloomington Stock Center and Julius Brennecke for providing flies. We thank Igor Antoshechkin (California Institute of Technology) for help with sequencing. This work was supported by grants from the National Research, Development and Innovation Office (NKFI-K117010, GINOP-2.3.2-15-2016-00032, and GINOP-2.3.2.-15-2016-00001) to (M.E. and F.J.), the NIH (R01 GM097363), the Ministry of Education and Science of the Russian Federation (14.W03.31.0007), and the Packard Fellowship Awards (to A.A.A.), and the NIH (R01GM110217) and Ellison Medical Foundation Awards (to K.F.T.). \n\nAuthor Contributions: M.N., A.A.A., and K.F.T. designed the experiments and wrote the manuscript. M.N., B.G., Y.L., Y.-C.A.C., and S.J.P. executed the experiments. F.J. and M.E. generated reagents. M.N. performed the computational analysis and interpretation of the data. \n\nThe authors declare no competing interests.\n\nAccepted Version - nihms-1548003.pdf
Submitted - 533232.full.pdf
Supplemental Material - 1-s2.0-S1097276519307592-mmc1.pdf
", "abstract": "\u0421hromatin is critical for genome compaction and gene expression. On a coarse scale, the genome is divided into euchromatin, which harbors the majority of genes and is enriched in active chromatin marks, and heterochromatin, which is gene-poor but repeat-rich. The conserved molecular hallmark of heterochromatin is the H3K9me3 modification, which is associated with gene silencing. We found that in Drosophila, deposition of most of the H3K9me3 mark depends on SUMO and the SUMO ligase Su(var)2-10, which recruits the histone methyltransferase complex SetDB1/Wde. In addition to repressing repeats, H3K9me3 influences expression of both hetero- and euchromatic host genes. High H3K9me3 levels in heterochromatin are required to suppress spurious transcription and ensure proper gene expression. In euchromatin, a set of conserved genes is repressed by Su(var)2-10/SetDB1-induced H3K9 trimethylation, ensuring tissue-specific gene expression. Several components of heterochromatin are themselves repressed by this pathway, providing a negative feedback mechanism to ensure chromatin homeostasis.", "date": "2020-02-06", "date_type": "published", "publication": "Molecular Cell", "volume": "77", "number": "3", "publisher": "Cell Press", "pagerange": "571-585", "id_number": "CaltechAUTHORS:20190130-121936593", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190130-121936593", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Research, Development and Innovation Office Hungary (NKFI)", "grant_number": "NKFI-K117010" }, { "agency": "National Research, Development and Innovation Office Hungary (NKFI)", "grant_number": "GINOP-2.3.2-15-2016-00032" }, { "agency": "National Research, Development and Innovation Office Hungary (NKFI)", "grant_number": "GINOP-2.3.2.-15-2016-00001" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "NIH", "grant_number": "R01GM110217" }, { "agency": "Ellison Medical Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.molcel.2019.09.033", "pmcid": "PMC7007874", "primary_object": { "basename": "1-s2.0-S1097276519307592-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/2st3h-t7d91/files/1-s2.0-S1097276519307592-mmc1.pdf" }, "related_objects": [ { "basename": "533232.full.pdf", "url": "https://authors.library.caltech.edu/records/2st3h-t7d91/files/533232.full.pdf" }, { "basename": "nihms-1548003.pdf", "url": "https://authors.library.caltech.edu/records/2st3h-t7d91/files/nihms-1548003.pdf" } ], "resource_type": "article", "pub_year": "2020", "author_list": "Ninova, Maria; Godneeva, Baira; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/bg38w-40s25", "eprint_id": 98949, "eprint_status": "archive", "datestamp": "2023-08-19 18:10:54", "lastmod": "2023-10-18 17:45:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "The control of gene expression and cell identity by H3K9 trimethylation", "ispublished": "pub", "full_text_status": "public", "keywords": "Chromatin, Heterochromatin, Epigenetics, Gene regulation, Transcriptional repression, Transposons, Germline, Cell fate maintenance", "note": "\u00a9 2019. Published by The Company of Biologists Ltd. \n\nPublished online September 20, 2019. \n\nWe thank the three reviewers for the insightful comments and suggestions that helped us to improve this article. The role of H3K9me3 in various aspects of gene regulation is a broad topic and we apologize to colleagues whose relevant work was not discussed due to space limitations. \n\nThe authors' research is supported by grants from the National Institutes of Health (R01 GM097363 to A.A.A. and R01 GM110217 to K.F.T.) and Minobrnauka of the Russian Federation (14.W03.31.0007), and by David and Lucile Packard Foundation Awards to A.A.A. Deposited in PMC for release after 12 months. \n\nThe authors declare no competing or financial interests.\n\nPublished - dev181180.full.pdf
", "abstract": "Histone 3 lysine 9 trimethylation (H3K9me3) is a conserved histone modification that is best known for its role in constitutive heterochromatin formation and the repression of repetitive DNA elements. More recently, it has become evident that H3K9me3 is also deposited at certain loci in a tissue-specific manner and plays important roles in regulating cell identity. Notably, H3K9me3 can repress genes encoding silencing factors, pointing to a fundamental principle of repressive chromatin auto-regulation. Interestingly, recent studies have shown that H3K9me3 deposition requires protein SUMOylation in different contexts, suggesting that the SUMO pathway functions as an important module in gene silencing and heterochromatin formation. In this Review, we discuss the role of H3K9me3 in gene regulation in various systems and the molecular mechanisms that guide the silencing machinery to target loci.", "date": "2019-10-01", "date_type": "published", "publication": "Development", "volume": "146", "number": "19", "publisher": "Company of Biologists", "pagerange": "Art. No. dev181180", "id_number": "CaltechAUTHORS:20190930-133755699", "issn": "0950-1991", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190930-133755699", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R01 GM110217" }, { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1242/dev.181180", "pmcid": "PMC6803365", "primary_object": { "basename": "dev181180.full.pdf", "url": "https://authors.library.caltech.edu/records/bg38w-40s25/files/dev181180.full.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Ninova, Maria; Fejes T\u00f3th, Katalin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rx4rz-bt148", "eprint_id": 99342, "eprint_status": "archive", "datestamp": "2023-08-19 16:39:14", "lastmod": "2023-10-18 18:14:34", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kuzmenko-A", "name": { "family": "Kuzmenko", "given": "A." } }, { "id": "Yudin-D", "name": { "family": "Yudin", "given": "D." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Ago nucleases from Clostridium butyricum and Limnothrix rosea can process DNA substrates at moderate temperatures", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors. FEBS Open Bio \u00a9 2019 FEBS. \n\nIssue Online: 04 July 2019. \n\nThis work was supported by the grant 14.W03.31.0007 of the Ministry of Science and Higher Education of the Russian Federation.\n\nPublished - Kuzmenko_2019p400.pdf
", "abstract": "Prokaryotic Argonaute proteins (pAgos) are diverse homologs of eukaryotic Argonautes (eAgos) involved in RNA interference. In contrast to eAgos, which are RNA-guided RNA nucleases, several pAgos were reported to act as DNA nucleases suggesting that they may be used as an alternative to CRISPRC as nucleases for\ngenome editing. However, all previously studied pAgos were isolated from thermophilic bacteria or archaea thus limiting their potential use in genomic applications. We describe two pAgo nucleases from mesophilic bacteria, Clostridium butyricum (CbAgo) and Limnothrix rosea (LrAgo). Both CbAgo and LrAgo use small DNA guides to cleave complementary DNA targets and are active at physiological temperatures. At the same time, the two proteins reveal significant variations in DNA processing depending on the reaction conditions and guide structure, including changes in the guide 5'-end and the presence of mismatches. We show that CbAgo is highly active under a wide range of conditions and can precisely cleave single-stranded\nand double-stranded DNA at moderate temperatures suggesting that it may be used for DNA manipulations both in vitro and in vivo.", "date": "2019-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "9", "number": "S1", "publisher": "Wiley", "pagerange": "400", "id_number": "CaltechAUTHORS:20191017-154306053", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191017-154306053", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12675", "primary_object": { "basename": "Kuzmenko_2019p400.pdf", "url": "https://authors.library.caltech.edu/records/rx4rz-bt148/files/Kuzmenko_2019p400.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Kuzmenko, A.; Yudin, D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/sy9vx-6rr07", "eprint_id": 99340, "eprint_status": "archive", "datestamp": "2023-08-19 16:39:05", "lastmod": "2023-10-18 18:14:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olina-A-V", "name": { "family": "Olina", "given": "A." } }, { "id": "Kudinova-A", "name": { "family": "Kudinova", "given": "A." } }, { "id": "Petrova-M", "name": { "family": "Petrova", "given": "M." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" }, { "id": "Esyunina-D", "name": { "family": "Esyunina", "given": "D." } } ] }, "title": "Catalytically active Argonaute nuclease from Synechococcus elongatus", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors. FEBS Open Bio \u00a9 2019 FEBS. \n\nIssue Online: 04 July 2019. \n\nThis work was supported by the grant 182907086 of the Russian Foundation for Basic Research.\n\nPublished - Olina_2019p160.pdf
", "abstract": "Argonaute proteins, which are found in almost all eukaryotes and in many prokaryotes, use small nucleic acid guides for the recognition and cleavage of complementary nucleic acids. While the role of eukaryotic Argonautes in RNA interference is well understood, the functions of prokaryotic Argonautes remain largely unknown. It was\nproposed that they may provide defense against invading nucleic acids, preferably acting on DNA targets. In this work, we studied the SynAgo protein from the cyanobacterium Synechococcus elongatus. We expressed affinity-tagged SynAgo in S. elongatus, purified the protein, and sequenced and mapped associated nucleic acids. We showed that SynAgo is bound with ~18 nt small DNAs coming from all genomic regions with no obvious gene specificity. Mass-spectrometry of copurified proteins from S. elongatus also revealed several possible protein partners of SynAgo. Biochemical analysis demonstrated that SynAgo is an active nuclease that can cleave both target DNA and RNA with varying efficiency, depending on the reaction conditions and the presence of mismatches between the guide and target strands. Finally, we introduced the SynAgo gene in the E. coli genome and tested its effects on plasmid maintenance and phage infections.", "date": "2019-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "9", "number": "S1", "publisher": "Wiley", "pagerange": "160", "id_number": "CaltechAUTHORS:20191017-152648736", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191017-152648736", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research (RFBR)", "grant_number": "18-29-07086" } ] }, "doi": "10.1002/2211-5463.12675", "primary_object": { "basename": "Olina_2019p160.pdf", "url": "https://authors.library.caltech.edu/records/sy9vx-6rr07/files/Olina_2019p160.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Olina, A.; Kudinova, A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/gs90z-www40", "eprint_id": 99343, "eprint_status": "archive", "datestamp": "2023-08-19 16:39:18", "lastmod": "2023-10-18 18:14:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yudin-D", "name": { "family": "Yudin", "given": "D." } }, { "id": "Ryazansky-S", "name": { "family": "Ryazansky", "given": "S." }, "orcid": "0000-0002-3171-2997" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" }, { "id": "Kuzmenko-A", "name": { "family": "Kuzmenko", "given": "A." } } ] }, "title": "Insights into genomic DNA sampling by prokaryotic Argonaute proteins", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors. FEBS Open Bio \u00a9 2019 FEBS. \n\nIssue Online: 04 July 2019. \n\nThis work was supported by the grant of the Ministry of Science and Higher Education of the Russian Federation 14.W03.31.0007.\n\nPublished - Yudin_2019p62.pdf
", "abstract": "Prokaryotic Argonaute proteins (pAgos) are endonucleases that bind small DNA or RNA guides and mediate cleavage of complementary targets. They are encoded in a variety of bacterial and archaeal genomes and supposedly participate in cell defence against foreign DNA. Previous biochemical and structural studies have elucidated the mechanistic aspects of guide binding, target search and cleavage by pAgos. pAgos have been shown to interfere with plasmid uptake in vivo and to autonomously produce guides from double-stranded DNA substrates in vitro. However, the principles underlying self/nonself discrimination remain unknown. Here we characterize in vivo guide biogenesis by pAgos from mesophilic bacteria Limnothrix rosea (LrAgo) and Clostridium butyricum (CbAgo). LrAgo and CbAgo are DNA-guided DNA endonucleases that copurify with small DNAs upon heterologous expression in E. coli. Such guide production depends on their catalytic activity and is abolished when pAgos are rendered inactive. Small DNAs originate from both the expression plasmid and the bacterial chromosome and are enriched for plasmid-derived sequences. Well-defined guide acquisition hotspots are observed within the host chromosome that likely correspond to the preferable sites of DNA processing by pAgos. The hotspots may presumably arise at sites of frequent DNA damage and repair and do not correlate with transcription levels at corresponding regions. Our observations suggest that pAgos may sample genomic DNA in a way similar to the CRISPR adaptation apparatus. As such the DNA repair machinery may orchestrate the action of prokaryotic defence systems by facilitating nonself targeting and guide acquisition.", "date": "2019-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "9", "number": "S1", "publisher": "Wiley", "pagerange": "62", "id_number": "CaltechAUTHORS:20191017-154712363", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191017-154712363", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12675", "primary_object": { "basename": "Yudin_2019p62.pdf", "url": "https://authors.library.caltech.edu/records/gs90z-www40/files/Yudin_2019p62.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Yudin, D.; Ryazansky, S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/dhtcd-14y14", "eprint_id": 99341, "eprint_status": "archive", "datestamp": "2023-08-19 16:39:10", "lastmod": "2023-10-18 18:14:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kropocheva-E", "name": { "family": "Kropocheva", "given": "E." } }, { "id": "Esyunina-D", "name": { "family": "Esyunina", "given": "D." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Various modes of nucleic acid processing by mesophilic bacterial Argonaute proteins", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors. FEBS Open Bio \u00a9 2019 FEBS. \n\nIssue Online: 04 July 2019. \n\nThis work was supported by the grant 14.W03.31.0007 of the Ministry of Science and Higher Education of the Russian Federation.\n\nPublished - Kropocheva_2019p159.pdf
", "abstract": "Argonaute (Ago) proteins are key components of RNA interference in eukaryotes, where they function as site-specific RNA nucleases guided by small noncoding RNAs and participate in post-transcriptional regulation. Many bacteria also encode Ago proteins but their functions and the mechanisms of action in bacterial cells remain unclear. We characterize in vitro biochemical properties of Ago proteins from several mesophilic bacteria, which can potentially be used as a tool for genome editing. Some of these proteins can bind small guide DNAs and act as DNA-dependent DNA nucleases, preferably acting on single-stranded DNA targets. We show that the preferred length of the guide DNAs bound by the Ago nucleases is 1520 nucleotides, and that single-nucleotide mismatches between the guide and target DNA strands can significantly affect the slicing activity, depending on the mismatch position. In particular, mismatches in the 3'-supplementary guide region decrease the cleavage efficiency, while mismatches in the seed region have a mild effect on the target cleavage. 5'-Phosphorylation of guides increases the rate and accuracy of target cleavage. The Ago proteins can catalyze DNA cleavage at the physiological range of temperatures (from < 25 \u2070C to 60 \u2070C), depending on the type and concentration of divalent cations in the reaction. Interestingly, some Agos can also utilize small RNA guides and/or cleave RNA targets. Thus, mesophilic Ago nucleases that have slicer activity at physiological temperatures are perspective candidates for development of new tools for manipulation with nucleic acids.", "date": "2019-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "9", "number": "S1", "publisher": "Wiley", "pagerange": "159", "id_number": "CaltechAUTHORS:20191017-153328759", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191017-153328759", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12675", "primary_object": { "basename": "Kropocheva_2019p159.pdf", "url": "https://authors.library.caltech.edu/records/dhtcd-14y14/files/Kropocheva_2019p159.pdf" }, "resource_type": "article", "pub_year": "2019", "author_list": "Kropocheva, E.; Esyunina, D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/943x8-mtw24", "eprint_id": 93230, "eprint_status": "archive", "datestamp": "2023-08-19 16:20:53", "lastmod": "2023-10-20 22:02:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kuzmenko-Anton", "name": { "family": "Kuzmenko", "given": "Anton" }, "orcid": "0000-0001-7169-0561" }, { "id": "Yudin-Denis", "name": { "family": "Yudin", "given": "Denis" }, "orcid": "0000-0002-4103-0543" }, { "id": "Ryazansky-Sergei", "name": { "family": "Ryazansky", "given": "Sergei" }, "orcid": "0000-0002-3171-2997" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Programmable DNA cleavage by Ago nucleases from mesophilic bacteria Clostridium butyricum and Limnothrix rosea", "ispublished": "pub", "full_text_status": "public", "keywords": "Argonaute proteins, DNA cleavage, CbAgo, LrAgo, CRISPR-Cas", "note": "\u00a9 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived: 21 February 2019; Revision Received: 27 April 2019; Accepted: 30 April 2019; Published: 22 May 2019. \n\nWe thank A. Oguienko for assistance with figure preparation, D. Esyunina and M. Petrova for experimental support and helpful discussions. \n\nFunding: Ministry of Science and Higher Education of the Russian Federation [14.W03.31.0007]. Funding for open access charge: Ministry of Science and Higher Education of the Russian Federation [14.W03.31.0007]. \n\nConflict of interest statement. None declared.\n\nPublished - gkz379.pdf
Submitted - 558684.full.pdf
Supplemental Material - gkz379_supplemental_files.pdf
", "abstract": "Argonaute (Ago) proteins are key players in RNA interference in eukaryotes, where they function as RNA-guided RNA endonucleases. Prokaryotic Argonautes (pAgos) are much more diverse than their eukaryotic counterparts but their cellular functions and mechanisms of action remain largely unknown. Some pAgos were shown to use small DNA guides for endonucleolytic cleavage of complementary DNA in vitro. However, previously studied pAgos from thermophilic prokaryotes function at elevated temperatures, which limits their potential use as a tool in genomic applications. Here, we describe two pAgos from mesophilic bacteria, Clostridium butyricum (CbAgo) and Limnothrix rosea (LrAgo), that act as DNA-guided DNA nucleases at physiological temperatures. In comparison with previously studied pAgos, CbAgo and LrAgo do not show strong preferences for the 5\u2032-nucleotide in guide DNA and can use not only 5\u2032-phosphorylated but also 5\u2032-hydroxyl DNA guides. Both CbAgo and LrAgo can tolerate guide/target mismatches in the seed region, but are sensitive to mismatches in the 3\u2032-guide region. Both pAgos can perform programmable endonucleolytic cleavage of double-stranded DNA substrates, showing enhanced activity at AT-rich regions and at elevated temperatures. The biochemical characterization of mesophilic pAgo proteins paves the way for their use for DNA manipulations both in vitro and in vivo.", "date": "2019-06-20", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "47", "number": "11", "publisher": "Oxford University Press", "pagerange": "5822-5836", "id_number": "CaltechAUTHORS:20190225-135750266", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190225-135750266", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1093/nar/gkz379", "pmcid": "PMC6582412", "primary_object": { "basename": "558684.full.pdf", "url": "https://authors.library.caltech.edu/records/943x8-mtw24/files/558684.full.pdf" }, "related_objects": [ { "basename": "gkz379.pdf", "url": "https://authors.library.caltech.edu/records/943x8-mtw24/files/gkz379.pdf" }, { "basename": "gkz379_supplemental_files.pdf", "url": "https://authors.library.caltech.edu/records/943x8-mtw24/files/gkz379_supplemental_files.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Kuzmenko, Anton; Yudin, Denis; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/f1naz-6r875", "eprint_id": 93222, "eprint_status": "archive", "datestamp": "2023-08-19 15:47:36", "lastmod": "2023-10-20 16:57:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kotov-Alexei-A", "name": { "family": "Kotov", "given": "Alexei A." }, "orcid": "0000-0002-5866-3574" }, { "id": "Adashev-Vladimir-E", "name": { "family": "Adashev", "given": "Vladimir E." } }, { "id": "Godneeva-Baira-K", "name": { "family": "Godneeva", "given": "Baira K." } }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Shatskikh-Aleksei-S", "name": { "family": "Shatskikh", "given": "Aleksei S." } }, { "id": "Bazylev-Sergei-S", "name": { "family": "Bazylev", "given": "Sergei S." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Olenina-Ludmila-V", "name": { "family": "Olenina", "given": "Ludmila V." }, "orcid": "0000-0002-7422-4387" } ] }, "title": "piRNA silencing contributes to interspecies hybrid sterility and reproductive isolation in Drosophila melanogaster", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived October 01, 2018; Revised February 12, 2019; Editorial Decision February 14, 2019; Accepted February 16, 2019. Published: 21 February 2019. \n\nData Availability: GEO accession number for the library data is GSE120802. \n\nWe thank the Developmental Studies Hybridoma Bank for maintaining some of the antibodies used in this study. We thank M. Siomi, E. Gracheva, R. Lehmann, and D. Dodt for antibodies and O. M. Olenkina for help with fly manipulations. We thank R. Sachidanandam for help with bioinformatics analysis. The authors thank the Common Use Center of scientific equipment of the Institute of Molecular Genetics RAS, for providing the equipment. \n\nFunding: Ministry of Education and Science of Russian Federation [14.W03.31.0007]. Funding for open access charge: Ministry of Education and Science of Russian Federation [14.W03.31.0007]. \n\nConflict of interest statement: None declared.\n\nPublished - gkz130.pdf
Supplemental Material - gkz130_supplemental_files.zip
", "abstract": "The piRNA pathway is an adaptive mechanism that maintains genome stability by repression of selfish genomic elements. In the male germline of Drosophila melanogaster repression of Stellate genes by piRNAs generated from Supressor of Stellate (Su(Ste)) locus is required for male fertility, but both Su(Ste) piRNAs and their targets are absent in other Drosophila species. We found that D. melanogaster genome contains multiple X-linked non-coding genomic repeats that have sequence similarity to the protein-coding host gene vasa. In the male germline, these vasa-related AT-chX repeats produce abundant piRNAs that are antisense to vasa; however, vasa mRNA escapes silencing due to imperfect complementarity to AT-chX piRNAs. Unexpectedly, we discovered AT-chX piRNAs target vasa of Drosophila mauritiana in the testes of interspecies hybrids. In the majority of hybrid flies, the testes were strongly reduced in size and germline content. A minority of hybrids maintained wild-type array of premeiotic germ cells in the testes, but in them harmful Stellate genes were derepressed due to the absence of Su(Ste) piRNAs, and meiotic failures were observed. Thus, the piRNA pathway contributes to reproductive isolation between D. melanogaster and closely related species, causing hybrid male sterility via misregulation of two different host protein factors.", "date": "2019-05-07", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "47", "number": "8", "publisher": "Oxford University Press", "pagerange": "4255-4271", "id_number": "CaltechAUTHORS:20190225-104840462", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190225-104840462", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1093/nar/gkz130", "pmcid": "PMC6486647", "primary_object": { "basename": "gkz130.pdf", "url": "https://authors.library.caltech.edu/records/f1naz-6r875/files/gkz130.pdf" }, "related_objects": [ { "basename": "gkz130_supplemental_files.zip", "url": "https://authors.library.caltech.edu/records/f1naz-6r875/files/gkz130_supplemental_files.zip" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Kotov, Alexei A.; Adashev, Vladimir E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/szdss-xw273", "eprint_id": 91436, "eprint_status": "archive", "datestamp": "2023-08-19 13:10:03", "lastmod": "2023-10-19 23:50:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-Lidiya", "name": { "family": "Lisitskaya", "given": "Lidiya" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-Andrey", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" } ] }, "title": "DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 the Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 2 February 2018 Accepted: 26 October 2018. Published: 04 December 2018. We apologize to many colleagues whose work is not cited due to space limitations. This work was supported by the Grant of the Ministry of Education and Science of Russian Federation 14.W03.31.0007. Author Contributions: L.L., A.A.A. and A.K. analyzed the data. L.L. and A.K. prepared the figures. A.A.A. and A.K. wrote the manuscript. Data availability: No datasets were generated or analysed during the current study. The authors declare no competing interests.
\n\nPublished - s41467-018-07449-7.pdf
Supplemental Material - 41467_2018_7449_MOESM1_ESM.pdf
", "abstract": "Recognition and repression of RNA targets by Argonaute proteins guided by small RNAs is the essence of RNA interference in eukaryotes. Argonaute proteins with diverse structures are also found in many bacterial and archaeal genomes. Recent studies revealed that, similarly to their eukaryotic counterparts, prokaryotic Argonautes (pAgos) may function in cell defense against foreign genetic elements but, in contrast, preferably act on DNA targets. Many crucial details of the pAgo action, and the roles of a plethora of pAgos with non-conventional architecture remain unknown. Here, we review available structural and biochemical data on pAgos and discuss their possible functions in host defense and other genetic processes in prokaryotic cells.", "date": "2018-12-04", "date_type": "published", "publication": "Nature Communications", "volume": "9", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 5165", "id_number": "CaltechAUTHORS:20181204-130810931", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181204-130810931", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1038/s41467-018-07449-7", "pmcid": "PMC6279821", "primary_object": { "basename": "41467_2018_7449_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/szdss-xw273/files/41467_2018_7449_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "s41467-018-07449-7.pdf", "url": "https://authors.library.caltech.edu/records/szdss-xw273/files/s41467-018-07449-7.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Lisitskaya, Lidiya; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/66qqd-2kg66", "eprint_id": 90173, "eprint_status": "archive", "datestamp": "2023-08-19 12:23:24", "lastmod": "2023-10-23 15:45:13", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ryazansky-S", "name": { "family": "Ryazansky", "given": "Sergei" }, "orcid": "0000-0002-3171-2997" }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "The expanded universe of prokaryotic Argonaute proteins", "ispublished": "pub", "full_text_status": "public", "keywords": "Ago, RNA interference, genome editing, horizontal gene transfer, prokaryotic Argonaute proteins", "note": "\u00a9 2018 Ryazansky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. \n\nReceived 3 September 2018; Accepted 20 November 2018; Published 18 December 2018. \n\nWe thank Mindaugas Margelevi\u010dius for the help with the prediction of PD-(D/E)XK motifs in proteins. \n\nThis work was supported by the grant of the Ministry of Education and Science of the Russian Federation 14.W03.31.0007.\n\nPublished - e01935-18.full.pdf
Submitted - 366930.full.pdf
Supplemental Material - inline-supplementary-material-1.pdf
Supplemental Material - inline-supplementary-material-2.xls
Supplemental Material - inline-supplementary-material-3.pdf
Supplemental Material - inline-supplementary-material-4.txt
Supplemental Material - inline-supplementary-material-5.pdf
Supplemental Material - inline-supplementary-material-6.txt
Supplemental Material - inline-supplementary-material-7.txt
Supplemental Material - inline-supplementary-material-8.xlsx
Supplemental Material - inline-supplementary-material-9.xls
", "abstract": "Members of the ancient family of Argonaute (Ago) proteins are present in all domains of life. The common feature of Ago proteins is the ability to bind small nucleic acid guides and use them for sequence-specific recognition\u2014and sometimes cleavage\u2014of complementary targets. While eukaryotic Ago (eAgo) proteins are key players in RNA interference and related pathways, the properties and functions of these proteins in archaeal and bacterial species have just started to emerge. We undertook comprehensive exploration of prokaryotic Ago (pAgo) proteins in sequenced genomes and revealed their striking diversity in comparison with eAgos. Many pAgos contain divergent variants of the conserved domains involved in interactions with nucleic acids, while having extra domains that are absent in eAgos, suggesting that they might have unusual specificities in the nucleic acid recognition and cleavage. Many pAgos are associated with putative nucleases, helicases, and DNA binding proteins in the same gene or operon, suggesting that they are involved in target processing. The great variability of pAgos revealed by our analysis opens new ways for exploration of their functions in host cells and for their use as potential tools in genome editing.", "date": "2018-11", "date_type": "published", "publication": "mBio", "volume": "9", "number": "6", "publisher": "American Society for Microbiology", "pagerange": "Art. No. e01935-18", "id_number": "CaltechAUTHORS:20181008-162020161", "issn": "2150-7511", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181008-162020161", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1128/mBio.01935-18", "pmcid": "PMC6299218", "primary_object": { "basename": "inline-supplementary-material-8.xlsx", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-8.xlsx" }, "related_objects": [ { "basename": "366930.full.pdf", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/366930.full.pdf" }, { "basename": "inline-supplementary-material-3.pdf", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-3.pdf" }, { "basename": "inline-supplementary-material-7.txt", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-7.txt" }, { "basename": "inline-supplementary-material-4.txt", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-4.txt" }, { "basename": "inline-supplementary-material-5.pdf", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-5.pdf" }, { "basename": "inline-supplementary-material-6.txt", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-6.txt" }, { "basename": "inline-supplementary-material-9.xls", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-9.xls" }, { "basename": "e01935-18.full.pdf", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/e01935-18.full.pdf" }, { "basename": "inline-supplementary-material-1.pdf", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-1.pdf" }, { "basename": "inline-supplementary-material-2.xls", "url": "https://authors.library.caltech.edu/records/66qqd-2kg66/files/inline-supplementary-material-2.xls" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Ryazansky, Sergei; Kulbachinskiy, Andrey; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zbrah-r0s55", "eprint_id": 87760, "eprint_status": "archive", "datestamp": "2023-08-21 23:40:15", "lastmod": "2023-10-18 21:25:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Liu-Yiwei", "name": { "family": "Liu", "given": "Yiwei" } }, { "id": "Esyunina-Daria-M", "name": { "family": "Esyunina", "given": "Daria" }, "orcid": "0000-0002-3706-4425" }, { "id": "Olovnikov-Ivan", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Teplova-Marianna", "name": { "family": "Teplova", "given": "Marianna" } }, { "id": "Kulbachinskiy-Andrey-V", "name": { "family": "Kulbachinskiy", "given": "Andrey" }, "orcid": "0000-0002-2292-6424" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Patel-Dinshaw-J", "name": { "family": "Patel", "given": "Dinshaw J." }, "orcid": "0000-0002-9779-7778" } ] }, "title": "Accommodation of Helical Imperfections in Rhodobacter sphaeroides Argonaute Ternary Complexes with Guide RNA and Target DNA", "ispublished": "pub", "full_text_status": "public", "keywords": "Rhodobacter sphaeroides Argonaute; RsAgo; guide RNA; target DNA; RNA-DNA heteroduplex; non-canonical base pairs and bulges", "note": "\u00a9 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). \n\nReceived 1 August 2017, Revised 11 April 2018, Accepted 5 June 2018, Available online 11 July 2018. \n\nOpen Access funded by National Institutes of Health. \n\nWe thank the synchrotron beamline staff at the Argonne National Laboratory for their assistance. D.J.P. was supported by NIH Grant TR01 GM104962; A.A.A. was supported by NIH Grants R01 GM097369, R00 HD057233, and DP2 OD007371A and a Searle Scholar Award; and D.E. and A.K. were supported by Russian Science Foundation Grant 16-14-10377. D.J.P. was supported by NIH Grant GM104962 and the Memorial Sloan Kettering Cancer Center Core Grant (P30 CA008748). \n\nAuthor Contributions: X-ray structure determination of RsAgo ternary complexes was performed by Y.L. and M.T. under the supervision of D.J.P. The identification of RsAgo specificity for gRNA and tDNA was performed by I.O. under the supervision of A.A.A. Analysis of interactions of RsAgo with guide and target molecules was performed by D.E. under the supervision of A.K. and A.A.A. \n\nThe authors declare no competing interests. \n\nData and Software Availability: The accession numbers for the ternary RsAgo complexes reported in this study are PDB: 6D8P (ternary RsAgo complex with fully paired gRNA-target DNA duplex), 6D92 (ternary RsAgo complex containing A3\u22c5A3\u2032 pair), 6D95 (ternary RsAgo complex containing A8\u22c5A8\u2032 pair), 6D9K (ternary RsAgo complex containing A8\u22c5G8\u2032 pair), 6D9L (ternary RsAgo complex containing G8\u22c5A8\u2032 pair), 6D8A (ternary RsAgo complex containing A-A bulge), and 6D8F (ternary RsAgo complex containing T-T bulge).\n\nPublished - 1-s2.0-S2211124718309161-main.pdf
Supplemental Material - 1-s2.0-S2211124718309161-mmc1.pdf
", "abstract": "Prokaryotic Argonaute (Ago) proteins were recently shown to target foreign genetic elements, thus making them a perfect model for studies of interference mechanisms. Here, we study interactions of Rhodobacter sphaeroides Ago (RsAgo) with guide RNA (gRNA) and fully complementary or imperfect target DNA (tDNA) using biochemical and structural approaches. We show that RsAgo can specifically recognize both the first nucleotide in gRNA and complementary nucleotide in tDNA, and both interactions contribute to nucleic acid binding. Non-canonical pairs and bulges on the target strand can be accommodated by RsAgo with minimal perturbation of the duplex but significantly reduce RsAgo affinity to tDNA. Surprisingly, mismatches between gRNA and tDNA induce dissociation of the guide-target duplex from RsAgo. Our results reveal plasticity in the ability of Ago proteins to accommodate helical imperfections, show how this might affect the efficiency of RNA silencing, and suggest a potential mechanism for guide release and Ago recycling.", "date": "2018-07-10", "date_type": "published", "publication": "Cell Reports", "volume": "24", "number": "2", "publisher": "Cell Press", "pagerange": "453-462", "id_number": "CaltechAUTHORS:20180711-124213871", "issn": "2211-1247", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180711-124213871", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "TR01 GM104962" }, { "agency": "NIH", "grant_number": "R01 GM097369" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "Russian Science Foundation", "grant_number": "16-14-10377" }, { "agency": "NIH", "grant_number": "GM104962" }, { "agency": "NIH", "grant_number": "P30 CA008748" } ] }, "doi": "10.1016/j.celrep.2018.06.021", "pmcid": "PMC6269105", "primary_object": { "basename": "1-s2.0-S2211124718309161-main.pdf", "url": "https://authors.library.caltech.edu/records/zbrah-r0s55/files/1-s2.0-S2211124718309161-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2211124718309161-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/zbrah-r0s55/files/1-s2.0-S2211124718309161-mmc1.pdf" } ], "resource_type": "article", "pub_year": "2018", "author_list": "Liu, Yiwei; Esyunina, Daria; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/074hc-asx29", "eprint_id": 88691, "eprint_status": "archive", "datestamp": "2023-08-19 10:03:38", "lastmod": "2023-10-18 22:14:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yudin-D", "name": { "family": "Yudin", "given": "D." } }, { "id": "Ryazansky-S", "name": { "family": "Ryazansky", "given": "S." }, "orcid": "0000-0002-3171-2997" }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kuzmenko-A", "name": { "family": "Kuzmenko", "given": "A." } } ] }, "title": "Catalytically active Argonaute proteins from mesophilic bacteria", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Federation of European Biochemical Societies. \n\nFirst Published: 05 July 2018. \n\nThis work was supported in part by the Grant of the Ministry of Education and Science of Russian Federation 14.W03.31.0007.\n\nPublished - Yudin_2018p127.pdf
", "abstract": "Argonaute proteins are an integral part of eukaryotic RNA interference machinery. They bind small noncoding RNAs and\nutilize them for guided cleavage of complementary RNA targets or indirect gene silencing by recruiting additional factors. Argonaute proteins are also encoded in many bacterial and archaeal genomes (pAgos). pAgos from thermophilic bacteria were initially studied to gain structural insight into eukaryotic RNA interference. They were later shown to cleave DNA substrates in a guided manner employing small RNAs or DNAs, which appear to be generated autonomously by pAgos. Thus, pAgos might be considered as means of prokaryotic defense against invasive genetic elements. Here we characterize pAgos from noncultivable or pathogenic mesophilic bacteria. Candidate proteins were selected through bioinformatic screening of genomic databases. Corresponding pAgo genes were chemically synthesized and used for expression in a heterologous system. Upon expression in E. coli these proteins have been shown to associate with short (1425 nt) 5'phosphorylated\nDNA molecules. Such short DNA loading relies on the catalytic activity of pAgos and is abolished in\ncatalytically dead protein variants, which bear amino acid substitutions in the DEDX catalytic tetrad. Further in\nvitro assays have shown that purified pAgos cleave various DNA substrates in a guidedependent manner. They display\nhigh activity at temperatures ranging from 30 to 45 \u00b0C, with the efficiency of cleavage being greatly affected by ionic strength, supplied divalent cations and guide molecules. This suggests that all studied pAgos act as DNA dependent DNA nucleases which may subsequently be used as means of targeted genome editing in eukaryotic organisms.", "date": "2018-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "8", "number": "S1", "publisher": "Wiley", "pagerange": "Art. No. P.01-071", "id_number": "CaltechAUTHORS:20180809-104828624", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180809-104828624", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12453", "primary_object": { "basename": "Yudin_2018p127.pdf", "url": "https://authors.library.caltech.edu/records/074hc-asx29/files/Yudin_2018p127.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Yudin, D.; Ryazansky, S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/qe3p2-qe339", "eprint_id": 88727, "eprint_status": "archive", "datestamp": "2023-08-19 10:03:53", "lastmod": "2023-10-18 22:16:11", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kropocheva-E", "name": { "family": "Kropocheva", "given": "E." } }, { "id": "Oguienko-A", "name": { "family": "Oguienko", "given": "A." } }, { "id": "Kudinova-A", "name": { "family": "Kudinova", "given": "A." } }, { "id": "Petrova-M", "name": { "family": "Petrova", "given": "M." } }, { "id": "Ryazansky-S", "name": { "family": "Ryazansky", "given": "S." }, "orcid": "0000-0002-3171-2997" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Functional activities of DNA-guided and RNA-guided bacterial Argonaute proteins", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Federation of European Biochemical Societies. \n\nFirst Published: 05 July 2018. \n\nThis work was supported by the Grant of the Ministry of Education and Science of Russian Federation 14.W03.31.0007.\n\nPublished - Kropocheva_2018p128.pdf
", "abstract": "Specific targeting of nucleic acids by Argonaute (Ago) proteins lies at the heart of RNA interference. Eukaryotic Ago's bind small RNAs and use them as guides for target RNA recognition and cleavage. Argonaute proteins are also found in bacterial and archaeal genomes where their roles remain unclear. Structural and biochemical studies of a few prokaryotic Ago proteins showed that they can function as endonucleases in vitro and may provide cell defense against foreign genetic elements in vivo. However, most prokaryotic Ago's are predicted to lack endonuclease activity; they also often have unusual domain architectures and are associated in the same operons with putative nucleases or helicases. In this study, we focused on prokaryotic Ago's from several cultivable bacterial species. We showed that although eukaryotic Ago's work only with RNA, prokaryotic proteins included in our analysis can use either RNA or DNA guides to recognize DNA targets. To define the specificity of bacterial Ago's we expressed them in Escherichia coli and analyzed associated short nucleic acids. Furthermore, we tested nucleolytic activity of three proteins in vitro using different guide and target molecules, and also measured the affinity of Ago's to guides and targets. The slicer activity of Ago's is known to depend on four conserved amino acid residues in the catalytic center. We showed that, in agreement with bioinformatic predictions, two of the three proteins possess the endonuclease activity. Our results indicate that bacterial Ago proteins\ncan cleave target nucleic acids with high specificity in vitro and can function in the heterologous E. coli system in vivo. These properties likely underlie the process of DNA/RNA interference in bacterial cells and may promote horizontal transfer of the Ago genes.", "date": "2018-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "8", "number": "S1", "publisher": "Wiley", "pagerange": "Art. No. P.01-074", "id_number": "CaltechAUTHORS:20180809-161421559", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180809-161421559", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12453", "primary_object": { "basename": "Kropocheva_2018p128.pdf", "url": "https://authors.library.caltech.edu/records/qe3p2-qe339/files/Kropocheva_2018p128.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Kropocheva, E.; Oguienko, A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/6bghx-pkt44", "eprint_id": 88715, "eprint_status": "archive", "datestamp": "2023-08-19 10:03:42", "lastmod": "2023-10-18 22:15:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Esyunina-D-M", "name": { "family": "Esyunina", "given": "D." }, "orcid": "0000-0002-3706-4425" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "M." }, "orcid": "0000-0001-5051-5502" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Highly specific target recognition by an Argonaute protein from Rhodobacter sphaeroides", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Federation of European Biochemical Societies. \n\nFirst Published: 05 July 2018. \n\nThis work was supported in part by the Russian Science Foundation (grant 161410377).\n\nPublished - Esyunina_2018p129.pdf
", "abstract": "Small noncoding RNAs play essential roles in genetic regulation in eukaryotic cells. In particular, several classes of small RNAs associate with proteins from the Argonaute (Ago) family to suppress the expression of complementary mRNA targets. Many bacteria also have Ago proteins, whose functions and the mechanism of action are poorly understood. Homology of prokaryotic Ago's with eukaryotic proteins makes them a promising model for structural and functional studies of the interference mechanisms. In our work we focused on the Ago protein from Rhodobacter sphaeroides (RsAgo) that was recently shown to use small RNA guides for targeting DNA. We demonstrated that RsAgo binds guide RNA (gRNA) with high affinity and found a single amino acid residue that participates in the specific recognition of the guide 5'nucleotide (U). We also measured the affinity of the RsAgogRNA complex to single-stranded target DNAs (tDNAs) with either full complementarity to the guide or with mismatches at each position. We found that fully complementary tDNA is bound with very high affinity, while mismatches both in the seed region close to the guide 5' end and in the downstream guide part significantly decrease target binding. Complexes of RsAgo with only gRNA or with gRNA and complementary tDNA are stable and reveal very limited exchange of nucleic acids over time. At the same time, we found that mismatches between gRNA and tDNA lead to dissociation of the guidetarget duplex from the RsAgo protein. We propose that this may serve as a mechanism for nucleic acid exchange in the cell, promoted by Ago interactions with non cognate targets. Our results reveal how complementarity between the guide and target strands affect the efficiency of target recognition and suggest a potential mechanism for guide release and Ago recycling.", "date": "2018-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "8", "number": "S1", "publisher": "Wiley", "pagerange": "Art. No. P.01-076", "id_number": "CaltechAUTHORS:20180809-144305720", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180809-144305720", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "161410377" } ] }, "doi": "10.1002/2211-5463.12453", "primary_object": { "basename": "Esyunina_2018p129.pdf", "url": "https://authors.library.caltech.edu/records/6bghx-pkt44/files/Esyunina_2018p129.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Esyunina, D.; Ninova, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/62m12-hzj53", "eprint_id": 88725, "eprint_status": "archive", "datestamp": "2023-08-19 10:03:48", "lastmod": "2023-10-18 22:16:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lisitskaya-L", "name": { "family": "Lisitskaya", "given": "L." } }, { "id": "Petushkov-I", "name": { "family": "Petushkov", "given": "I." } }, { "id": "Esyunina-D", "name": { "family": "Esyunina", "given": "D." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Kulbachinskiy-A", "name": { "family": "Kulbachinskiy", "given": "A." }, "orcid": "0000-0002-2292-6424" } ] }, "title": "Interactions of a bacterial Argonaute protein with DNA targets in vitro", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Federation of European Biochemical Societies. \n\nFirst Published: 05 July 2018. \n\nThis work was supported in part by the Grant of the Ministry of Education and Science of Russian Federation 14.W03.31.0007.\n\nPublished - Lisitskaya_2018p420.pdf
", "abstract": "Argonaute proteins are central components of RNA interference in eukaryotes but the functions of homologous proteins in prokaryotes remain largely unknown. Rhodobacter sphaeroides Argonaute protein (RsAgo) was shown to\npreferentially recognize foreign genetic elements in vivo suggesting its role in RNA interference in bacterial cells. RsAgo was proposed to use guide RNAs to recognize complementary target DNA, leading to inhibition of transcription and also its nucleolytic cleavage by accessory nucleases. However, the mechanisms of specific DNA targeting by RsAgo and, in particular, the details of its interactions with double-stranded DNA molecules are unknown. In the present study, we analyzed the interactions of guide-loaded RsAgo with dsDNA targets in vitro. Using the gel shift assay, we showed that successful loading of RsAgo onto dsDNA requires prior DNA melting. The boundaries of the assembled ternary complex of RsAgo with guide RNA and dsDNA were revealed by footprinting methods. Possible interactions of RsAgo with RNA polymerases of Escherichia coli and R. sphaeroides were tested using the bacterial two-hybrid system, and the domains of the \u03b2 and \u03b2'-subunits\nof RNA polymerase that are likely involved in interactions with RsAgo were identified. The results suggest that recognition of dsDNA targets by RsAgo in vivo may be facilitated by DNA replication and/or transcription, a hypothesis that is now under investigation.", "date": "2018-07", "date_type": "published", "publication": "FEBS Open Bio", "volume": "8", "number": "S1", "publisher": "Wiley", "pagerange": "Art. No. P.18-108", "id_number": "CaltechAUTHORS:20180809-153622993", "issn": "2211-5463", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180809-153622993", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" } ] }, "doi": "10.1002/2211-5463.12453", "primary_object": { "basename": "Lisitskaya_2018p420.pdf", "url": "https://authors.library.caltech.edu/records/62m12-hzj53/files/Lisitskaya_2018p420.pdf" }, "resource_type": "article", "pub_year": "2018", "author_list": "Lisitskaya, L.; Petushkov, I.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/94s84-5v602", "eprint_id": 86493, "eprint_status": "archive", "datestamp": "2023-08-21 23:17:26", "lastmod": "2023-10-18 19:39:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olina-A-V", "name": { "family": "Olina", "given": "A. V." } }, { "id": "Kulbachinskiy-A-V", "name": { "family": "Kulbachinskiy", "given": "A. V." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Esyunina-D-M", "name": { "family": "Esyunina", "given": "D. M." } } ] }, "title": "Argonaute Proteins and Mechanisms of RNA Interference in Eukaryotes and Prokaryotes", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Argonaute proteins; RNA interference; small RNAs; mobile genetic elements", "note": "\u00a9 2018 Pleiades Publishing, Ltd. \n\nReceived November 8, 2017; Revision received December 5, 2017; First Online: 19 May 2018. \n\nThis work was supported by the Russian Science Foundation (grant 16-14-10377).", "abstract": "Noncoding RNAs play essential roles in genetic regulation in all organisms. In eukaryotic cells, many small non-coding RNAs act in complex with Argonaute proteins and regulate gene expression by recognizing complementary RNA targets. The complexes of Argonaute proteins with small RNAs also play a key role in silencing of mobile genetic elements and, in some cases, viruses. These processes are collectively called RNA interference. RNA interference is a powerful tool for specific gene silencing in both basic research and therapeutic applications. Argonaute proteins are also found in prokaryotic organisms. Recent studies have shown that prokaryotic Argonautes can also cleave their target nucleic acids, in particular DNA. This activity of prokaryotic Argonautes might potentially be used to edit eukaryotic genomes. However, the molecular mechanisms of small nucleic acid biogenesis and the functions of Argonaute proteins, in particular in bacteria and archaea, remain largely unknown. Here we briefly review available data on the RNA interference processes and Argonaute proteins in eukaryotes and prokaryotes.", "date": "2018-05", "date_type": "published", "publication": "Biochemistry (Moscow)", "volume": "83", "number": "5", "publisher": "Springer", "pagerange": "483-497", "id_number": "CaltechAUTHORS:20180521-094519332", "issn": "0006-2979", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180521-094519332", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Science Foundation", "grant_number": "16-14-10377" } ] }, "doi": "10.1134/S0006297918050024", "resource_type": "article", "pub_year": "2018", "author_list": "Olina, A. V.; Kulbachinskiy, A. V.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/a8hdk-00724", "eprint_id": 81908, "eprint_status": "archive", "datestamp": "2023-08-19 05:47:41", "lastmod": "2023-10-17 21:55:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Huang-Xiawei", "name": { "family": "Huang", "given": "Xiawei" }, "orcid": "0000-0001-9084-0510" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "piRNA Biogenesis in Drosophila melanogaster", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Elsevier Ltd. \n\nAvailable online 27 September 2017. \n\nThis work was supported by grants from the National Institutes of Health R01 GM097363, R01 GM110217, the Ministry of Education and Science of the Russian Federation 14.W03.31.0007, and the HHMI Scholar and Packard Fellowship awards.\n\nAccepted Version - nihms909375.pdf
", "abstract": "The PIWI-interacting RNA (piRNA) pathway is a conserved defense system that protects the genome integrity of the animal germline from deleterious transposable elements. Targets of silencing are recognized by small noncoding piRNAs that are processed from long precursor molecules. Although piRNAs and other classes of small noncoding RNAs, such as miRNAs and small interfering (si)RNAs, interact with members of the same family of Argonaute (Ago) proteins and their function in target repression is similar, the biogenesis of piRNAs differs from those of the other two small RNAs. Recently, many aspects of piRNA biogenesis have been revealed in Drosophila melanogaster. In this review, we elaborate on piRNA biogenesis in Drosophila somatic and germline cells. We focus on the mechanisms by which piRNA precursor transcription is regulated and highlight recent work that has advanced our understanding of piRNA precursor processing to mature piRNAs. We finish by discussing current models to the still unresolved question of how piRNA precursors are selected and channeled into the processing machinery.", "date": "2017-11", "date_type": "published", "publication": "Trends in Genetics", "volume": "33", "number": "11", "publisher": "Cell Press", "pagerange": "882-894", "id_number": "CaltechAUTHORS:20170928-154519998", "issn": "0168-9525", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170928-154519998", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R01 GM110217" }, { "agency": "Ministry of Education and Science of the Russian Federation", "grant_number": "14.W03.31.0007" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1016/j.tig.2017.09.002", "pmcid": "PMC5773129", "primary_object": { "basename": "nihms909375.pdf", "url": "https://authors.library.caltech.edu/records/a8hdk-00724/files/nihms909375.pdf" }, "resource_type": "article", "pub_year": "2017", "author_list": "Huang, Xiawei; Fejes T\u00f3th, Katalin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b88cv-24x67", "eprint_id": 79106, "eprint_status": "archive", "datestamp": "2023-08-19 03:44:41", "lastmod": "2023-10-26 14:35:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bamezai-S", "name": { "family": "Bamezai", "given": "S." } }, { "id": "Mulaw-M", "name": { "family": "Mulaw", "given": "M." } }, { "id": "Vegi-N", "name": { "family": "Vegi", "given": "N." } }, { "id": "Feuring-Buske-M", "name": { "family": "Feuring-Buske", "given": "M." } }, { "id": "Zhou-F", "name": { "family": "Zhou", "given": "F." } }, { "id": "Rohde-C", "name": { "family": "Rohde", "given": "C." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A." } }, { "id": "Hoell-J", "name": { "family": "Hoell", "given": "J." } }, { "id": "Kloetgen-A", "name": { "family": "Kloetgen", "given": "A." } }, { "id": "Borkhardt-A", "name": { "family": "Borkhardt", "given": "A." } }, { "id": "Plass-C", "name": { "family": "Plass", "given": "C." } }, { "id": "M\u00fcller-Tidow-C", "name": { "family": "M\u00fcller-Tidow", "given": "C." } }, { "id": "Rawat-V-P", "name": { "family": "Rawat", "given": "V. P." } }, { "id": "Buske-C", "name": { "family": "Buske", "given": "C." } } ] }, "title": "PIWIL4 Acts as a piRNA Binding, Epigenetically Active and Growth Regulatory Protein in Human Acute Myeloid Leukemia", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 by the Ferrata Storti Foundation.\n\nPublished - Bamezai_2017p154.pdf
", "abstract": "Piwi proteins are critically important for maintaining the self-renewing stem cell population in lower organisms through epigenetic silencing of transposable elements via DNA methylation and H3K9me3 marks, in close interaction with a novel class of non-coding RNA called piwi interacting RNA (piRNA).", "date": "2017-06-26", "date_type": "published", "publication": "Haematologica", "volume": "102", "number": "S2", "publisher": "Ferrata Storti Foundation", "pagerange": "Art. No. S429", "id_number": "CaltechAUTHORS:20170714-085839589", "issn": "0390-6078", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170714-085839589", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "primary_object": { "basename": "Bamezai_2017p154.pdf", "url": "https://authors.library.caltech.edu/records/b88cv-24x67/files/Bamezai_2017p154.pdf" }, "resource_type": "article", "pub_year": "2017", "author_list": "Bamezai, S.; Mulaw, M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kzg6r-s6q65", "eprint_id": 77184, "eprint_status": "archive", "datestamp": "2023-08-19 03:18:21", "lastmod": "2023-10-25 21:57:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ciabrelli-Filippo", "name": { "family": "Ciabrelli", "given": "Filippo" }, "orcid": "0000-0001-7064-4723" }, { "id": "Comoglio-Federico", "name": { "family": "Comoglio", "given": "Federico" }, "orcid": "0000-0002-8970-6610" }, { "id": "Fellous-Simon", "name": { "family": "Fellous", "given": "Simon" }, "orcid": "0000-0003-3921-4578" }, { "id": "Bonev-Boyan", "name": { "family": "Bonev", "given": "Boyan" }, "orcid": "0000-0002-7502-9399" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Szabo-Quentin", "name": { "family": "Szabo", "given": "Quentin" }, "orcid": "0000-0002-3539-7875" }, { "id": "Xu\u00e9reb-Anne", "name": { "family": "Xu\u00e9reb", "given": "Anne" }, "orcid": "0000-0003-1728-0785" }, { "id": "Klopp-Christophe", "name": { "family": "Klopp", "given": "Christophe" }, "orcid": "0000-0001-7126-5477" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Paro-Renato", "name": { "family": "Paro", "given": "Renato" }, "orcid": "0000-0003-3308-2965" }, { "id": "Bantignies-Fr\u00e9d\u00e9ric", "name": { "family": "Bantignies", "given": "Fr\u00e9d\u00e9ric" }, "orcid": "0000-0003-4063-7324" }, { "id": "Cavalli-Giacomo", "name": { "family": "Cavalli", "given": "Giacomo" }, "orcid": "0000-0003-3709-3469" } ] }, "title": "Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Macmillan Publishers Limited, part of Springer Nature. \n\nReceived 09 August 2016; Accepted 27 March 2017; Published online 24 April 2017. \n\nThis study benefited from the CNRS human and technical resources allocated to the ECOTRONS Research Infrastructure as well as from the state allocation 'Investissement d'Avenir' AnaEE-France ANR-11-INBS-0001. We thank J. Roy, S. Devidal, A. Milcu, D. Landais, O. Ravel and A. Faez for assistance at the Ecotron-CNRS Facility in Montpellier; J. Foucaud, B. Serrate and A. Rombaut for assistance with conducting experiments on environmental effects in CBGP; J.-M. Chang and V. Loubiere for technical support; M. Siomi (Keio University) for providing the anti-Aubergine 4D10 antibody; and the Montpellier Ressources Imagerie facility MRI-IGH for microscopy support. F. Ciabrelli was supported by the Fondation pour la Recherche M\u00e9dicale (FRM). F.B. was supported by CNRS. F. Comoglio was supported by ETH Zurich. B.B. was supported by the Sir Henry Wellcome Postdoctoral Fellowship (WT100136MA). The research of R.P. was supported by the FP7 European Network of Excellence EpiGeneSys, the Swiss National Science Foundation and ETH Zurich. M.N. and A.A. were supported by NIH R01 grant GM097363. Research in the laboratory of G.C. was supported by grants from the European Research Council (ERC-2008-AdG no. 232947), the CNRS, the FP7 European Network of Excellence EpiGeneSys, the European Union's Horizon 2020 Research and Innovation Programme under grant agreement 676556 (MuG), the Agence Nationale de la Recherche, the Fondation pour la Recherche M\u00e9dicale, the INSERM, the French National Cancer Institute (INCa) and the Laboratory of Excellence EpiGenMed. \n\nAuthor Contributions: F. Ciabrelli and G.C. initiated and led the project. F. Ciabrelli designed and performed the experiments. F. Ciabrelli and G.C. interpreted the data. F. Ciabrelli and F.B. performed the FISH-I experiments. F. Ciabrelli, F.B. and Q.S. analyzed and interpreted the FISH-I data. F. Ciabrelli and F.B. performed the Antp[Ns] genetic crosses, scored the phenotypes and interpreted the data. F. Ciabrelli, S.F. and G.C. designed the experiments on environmental effects and interpreted the data. F. Ciabrelli, S.F. and A.X. performed the experiments on environmental effects. F. Comoglio analyzed genomic DNA sequencing data and performed bioinformatic analyses. C.K. analyzed sequencing data on the transgenic region. B.B. analyzed RNA-sequencing data and performed bioinformatic analyses. M.N. analyzed small-RNA-sequencing data and performed bioinformatic analyses. F. Ciabrelli, F.B., F. Comoglio, A.A., R.P. and G.C. wrote the manuscript. All the authors reviewed and commented on the manuscript. \n\nThe authors declare no competing financial interests.\n\nAccepted Version - nihms863505.pdf
Supplemental Material - ng.3848-S1.pdf
Supplemental Material - ng.3848-S2.xlsx
Supplemental Material - ng.3848-S3.xlsx
Supplemental Material - ng.3848-S4.xlsx
Supplemental Material - ng.3848-S5.xlsx
", "abstract": "Transgenerational epigenetic inheritance (TEI) describes the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known about the principles and the molecular mechanisms governing this type of inheritance. Here, by transiently enhancing 3D chromatin interactions, we established stable and isogenic Drosophila epilines that carry alternative epialleles, as defined by differential levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming H3K27me3). After being established, epialleles can be dominantly transmitted to naive flies and can induce paramutation. Importantly, epilines can be reset to a naive state by disruption of chromatin interactions. Finally, we found that environmental changes modulate the expressivity of the epialleles, and we extended our paradigm to naturally occurring phenotypes. Our work sheds light on how nuclear organization and Polycomb group (PcG) proteins contribute to epigenetically inheritable phenotypic variability.", "date": "2017-06", "date_type": "published", "publication": "Nature Genetics", "volume": "49", "number": "6", "publisher": "Nature Publishing Group", "pagerange": "876-886", "id_number": "CaltechAUTHORS:20170504-075656920", "issn": "1061-4036", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170504-075656920", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Agence Nationale pour la Recherche (ANR)", "grant_number": "ANR-11-INBS-0001" }, { "agency": "Fondation pour la Recherche M\u00e9dicale" }, { "agency": "Centre National de la Recherche Scientifique (CNRS)" }, { "agency": "ETH Zurich" }, { "agency": "Wellcome Trust", "grant_number": "WT100136MA" }, { "agency": "European Union", "grant_number": "EpiGeneSys" }, { "agency": "Swiss National Science Foundation (SNSF)" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "European Research Council (ERC)", "grant_number": "232947" }, { "agency": "European Research Council (ERC)", "grant_number": "676556" }, { "agency": "Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (INSERM)" }, { "agency": "Institut National du Cancer" }, { "agency": "Laboratory of Excellence", "grant_number": "EpiGenMed" } ] }, "collection": "CaltechAUTHORS", "doi": "10.1038/ng.3848", "pmcid": "PMC5484582", "primary_object": { "basename": "ng.3848-S2.xlsx", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/ng.3848-S2.xlsx" }, "related_objects": [ { "basename": "ng.3848-S1.pdf", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/ng.3848-S1.pdf" }, { "basename": "ng.3848-S3.xlsx", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/ng.3848-S3.xlsx" }, { "basename": "ng.3848-S4.xlsx", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/ng.3848-S4.xlsx" }, { "basename": "ng.3848-S5.xlsx", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/ng.3848-S5.xlsx" }, { "basename": "nihms863505.pdf", "url": "https://authors.library.caltech.edu/records/kzg6r-s6q65/files/nihms863505.pdf" } ], "resource_type": "article", "pub_year": "2017", "author_list": "Ciabrelli, Filippo; Comoglio, Federico; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zg6en-0bx88", "eprint_id": 67909, "eprint_status": "archive", "datestamp": "2023-08-20 12:48:00", "lastmod": "2023-10-19 22:04:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Stuwe-Evelyn", "name": { "family": "Stuwe", "given": "Evelyn" } }, { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Le-Thomas-Adrien", "name": { "family": "Le Thomas", "given": "Adrien" }, "orcid": "0000-0002-9526-3916" }, { "id": "Rozhavskaya-Ekaterina", "name": { "family": "Rozhavskaya", "given": "Ekaterina" } }, { "id": "Li-Sisi", "name": { "family": "Li", "given": "Sisi" } }, { "id": "Vempati-Sivani", "name": { "family": "Vempati", "given": "Sivani" } }, { "id": "Laver-John-D", "name": { "family": "Laver", "given": "John D." } }, { "id": "Patel-Dinshaw-J", "name": { "family": "Patel", "given": "Dinshaw J." }, "orcid": "0000-0002-9779-7778" }, { "id": "Smibert-Craig-A", "name": { "family": "Smibert", "given": "Craig A." } }, { "id": "Lipshitz-Howard-D", "name": { "family": "Lipshitz", "given": "Howard D." }, "orcid": "0000-0002-7372-4419" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Cutoff Suppresses RNA Polymerase II Termination to Ensure Expression of piRNA Precursors", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 Elsevier Inc. \n\nReceived: December 28, 2015; Revised: April 4, 2016; Accepted: May 6, 2016; Published: June 9, 2016. \n\nWe thank members of the A.A.A. lab for discussion. We thank Igor Antoshechkin (Caltech) for help with sequencing and Sergei Manakov for processing the RNA-seq data. E.S. was supported by a PhD fellowship of the Boehringer Ingelheim Fonds. This work was supported by grants from the NIH (R01 GM097363 and DP2 OD007371A), by the Searle Scholar and the Packard Fellowship Awards to A.A.A., by a Ellison Medical Foundation award to K.F.T., grants from the Canadian Institutes of Health Research (MOP-14409) and the Natural Sciences and Engineering Research Council of Canada (RGPIN-201) to H.D.L., a grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-435985) to C.A.S., and by funds from the Abby Rockefeller Mauze Trust and Maloris and STARR Foundations to D.J.P. \n\nAuthor Contributions: \nExperiments were designed and performed by Y.-C.A.C. piRNA-seq, total RNA-seq, and polyA RNA-seq in Figures 1 and 2A, and Figures 2C, 2D, 4B, 4C, 4E, 4F, 4H, 6A, 6B, 6E, 7A\u20137C, and 7E\u20137G, E.S. GRO-seq and chromRNA-seq in Figures 1, 2A, 2B, and 3, Y.L. Figures 2D, 4D, 4G, 5, 6C, 6D, and 7D, A.L.T. Pld promoter deletion and piRNA analysis, Figure 2A, with help from E.R. and S.V. All bioinformatic analysis was performed by M.N., and S.L. and D.J.P. modeled the Cuff structure. J.D.L., C.A.S., and H.D.L. generated the CBP80 antibody. A.A.A. and K.F.T. aided in study design and data interpretation. Y.-C.A.C. and A.A.A. wrote the paper with input from E.S., M.N., Y.L., and K.F.T.\n\nAccepted Version - nihms-795577.pdf
Supplemental Material - mmc1.pdf
", "abstract": "Small non-coding RNAs called piRNAs serve as guides for an adaptable immune system that represses transposable elements in germ cells of Metazoa. In Drosophila the RDC complex, composed of Rhino, Deadlock and Cutoff (Cuff) bind chromatin of dual-strand piRNA clusters, special genomic regions, which encode piRNA precursors. The RDC complex is required for transcription of piRNA precursors, though the mechanism by which it licenses transcription remained unknown. Here, we show that Cuff prevents premature termination of RNA polymerase II. Cuff prevents cleavage of nascent RNA at poly(A) sites by interfering with recruitment of the cleavage and polyadenylation specificity factor (CPSF) complex. Cuff also protects processed transcripts from degradation by the exonuclease Rat1. Our work reveals a conceptually different mechanism of transcriptional enhancement. In contrast to other factors that regulate termination by binding to specific signals on nascent RNA, the RDC complex inhibits termination in a chromatin-dependent and sequence-independent manner.", "date": "2016-07-07", "date_type": "published", "publication": "Molecular Cell", "volume": "63", "number": "1", "publisher": "Cell Press", "pagerange": "97-109", "id_number": "CaltechAUTHORS:20160614-103714874", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160614-103714874", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Boehringer Ingelheim Fonds" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Ellison Medical Foundation" }, { "agency": "Canadian Institutes of Health Research", "grant_number": "MOP-14409" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)", "grant_number": "RGPIN-201" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)", "grant_number": "RGPIN-435985" }, { "agency": "Abby Rockefeller Mauze Trust" }, { "agency": "Maloris Foundation" }, { "agency": "STARR Foundation" } ] }, "doi": "10.1016/j.molcel.2016.05.010", "pmcid": "PMC4980073", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/zg6en-0bx88/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms-795577.pdf", "url": "https://authors.library.caltech.edu/records/zg6en-0bx88/files/nihms-795577.pdf" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Chen, Yung-Chia Ariel; Stuwe, Evelyn; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/z6cr3-qm212", "eprint_id": 66455, "eprint_status": "archive", "datestamp": "2023-08-22 17:44:05", "lastmod": "2023-10-18 18:06:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hur-Junho-K", "name": { "family": "Hur", "given": "Junho K." }, "orcid": "0000-0003-3794-1149" }, { "id": "Luo-Yicheng", "name": { "family": "Luo", "given": "Yicheng" }, "orcid": "0000-0003-3704-2389" }, { "id": "Moon-Sungjin", "name": { "family": "Moon", "given": "Sungjin" } }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Marinov-Georgi-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Chung-Yun-D", "name": { "family": "Chung", "given": "Yun D." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila", "ispublished": "pub", "full_text_status": "public", "keywords": "TREX; Thoc5; mRNA loading; piRNA biogenesis; transcriptional regulation", "note": "\u00a9 2016 Hur et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International, as described at http://creativecommons.org/licenses/by-nc/4.0/. \n\nReceived December 6, 2015; revised version accepted March 7, 2016. \n\nWe greatly thank Katalin Fejes Toth for discussion and help with manuscript preparation.We thank members of the Aravin laboratory for discussion and comments on the manuscript. We thank Sergei Manakov for processing the RNA-seq data, and Jang-Hyun Oh for help in coimmunoprecipitation experiments. We thank Masakazu Hamada for establishing and optimizing the protocol for isolation of chromatin-associated RNA. We thank Long Cai and Kelly Burke for help with FISH. This work was supported by grants from the National Institutes of Health (R01 GM097363 and DP2 OD007371A) as well as by the Searle Scholar and the Packard Fellowship Awards to A.A.A., and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (no. 2015R1A2A2A01003598) to Y.D.C.\n\nPublished - Genes_Dev.-2016-Hur-840-55.pdf
Supplemental Material - Supp_Legends_Figures.pdf
Supplemental Material - Supp_TableS1.xlsx
Supplemental Material - Supp_TableS2.xlsx
Supplemental Material - Supp_TableS3.pdf
Supplemental Material - Supp_TableS4.pdf
Supplemental Material - Supp_TableS5.xlsx
Supplemental Material - Supp_TableS6.pdf
", "abstract": "The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis.", "date": "2016-04-01", "date_type": "published", "publication": "Genes and Development", "volume": "30", "number": "7", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "840-855", "id_number": "CaltechAUTHORS:20160425-132521525", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160425-132521525", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "National Research Foundation of Korea" }, { "agency": "Ministry of Science, ICT and Future Planning (Korea)", "grant_number": "2015R1A2A2A01003598" } ] }, "doi": "10.1101/gad.276030.115", "pmcid": "PMC4826399", "primary_object": { "basename": "Supp_TableS2.xlsx", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS2.xlsx" }, "related_objects": [ { "basename": "Supp_TableS3.pdf", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS3.pdf" }, { "basename": "Supp_TableS4.pdf", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS4.pdf" }, { "basename": "Supp_TableS5.xlsx", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS5.xlsx" }, { "basename": "Supp_TableS6.pdf", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS6.pdf" }, { "basename": "Genes_Dev.-2016-Hur-840-55.pdf", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Genes_Dev.-2016-Hur-840-55.pdf" }, { "basename": "Supp_Legends_Figures.pdf", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_Legends_Figures.pdf" }, { "basename": "Supp_TableS1.xlsx", "url": "https://authors.library.caltech.edu/records/z6cr3-qm212/files/Supp_TableS1.xlsx" } ], "resource_type": "article", "pub_year": "2016", "author_list": "Hur, Junho K.; Luo, Yicheng; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/jjax6-csn88", "eprint_id": 63373, "eprint_status": "archive", "datestamp": "2023-08-22 17:01:48", "lastmod": "2023-10-25 23:46:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cheloufi-Sihem", "name": { "family": "Cheloufi", "given": "Sihem" }, "orcid": "0000-0002-1726-4796" }, { "id": "Ninova-Maria", "name": { "family": "Ninova", "given": "Maria" }, "orcid": "0000-0001-5051-5502" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "The histone chaperone CAF-1 safeguards somatic cell identity", "ispublished": "pub", "full_text_status": "public", "keywords": "Pluripotent stem cells; Reprogramming; Induced pluripotent stem cells", "note": "\u00a9 2015 Macmillan Publishers Limited. \n\nReceived 23 February 2015; Accepted 28 September 2015. Published online 09 December 2015. \n\nWe thank B. Kingston, C. Vakoc, M. Tolstorukov and G. Hannon for guidance and discussions, B. Bernstein, K. Plath, K. Chronis, Y. Shen and O. Tam for advice on the ATAC-seq analysis, P. Brown for providing the Dot1l inhibitor, B. Stillman for sharing the Chaf1b antibody and T. Graf for sharing the C10 cell line. We thank C. Nakada and Y. Kiyota (Nikon) for providing software to quantify iPS cell formation and A. Huebner for help with transdifferentiation experiments. We are grateful to H. Hock and the HSCI-CRM flow cytometry core for help with flow data analysis and to W. Mallard for initial RNA-sequencing analysis. We further thank B. Ma, S. Muller, M. Weissenboeck and the IMP/IMBA Biooptics and Transgenic core facility as well the CSF NGS laboratory for technical assistance and all members of the Hochedlinger, Zuber, Penninger, Elling, Shi and Kingston laboratories for their feedback on various aspects of this project. We thank A. Stark, A. Deaton and L. Barrett for critical reading of the manuscript. S.C. was supported by the PRCRP at the Department of Defense (CA 120212). H.Y.C. by was supported by NIH P50-HG007735. U.E. was funded by grants from IMBA and the Austrian National Foundation. S.W.L. was supported by a cancer center support grant and program project grant from the NCI and is an HHMI investigator. J.M.P. was supported by IMBA, ERC GA (number 341036) and the Innovator Award/Era of Hope Award Number W81XWH-12-1-0093. J.Z. was funded by an ERC starting grant (number 336860) and generous institutional funding from Boehringer Ingelheim. K.H. was supported by funds from the MGH, HHMI, NIH (R01 HD058013-06) and the Gerald and Darlene Jordan Chair in Regenerative Medicine. \n\nAuthor Contributions: Y. L. Jung and B. Hopfgartner contributed equally to this work. S.C., K.H., U.E. and J.Z. designed primary screens, analysed and interpreted data. S.C., J.M. and N.A. performed the arrayed screen and S.C. conducted follow-up cell biology and chromatin studies. U.E. and B.H. performed the multiplexed screen. U.E. performed validation experiments, genetic interaction assays and cell biology experiments with support from B.H., M.H. and D.W. Human reprogramming experiments were performed by S.C. and J.B.; N.T. and S.W.L. assisted in the generation of inducible Col1a1::tetOP-Chaf1a shRNA cell lines. S.C., A.I.B., A.B. and Y.S. performed B-cell to macrophage conversion experiments. C.E.A. and M.W. conducted MEF to induced neuron transdifferentiation experiments. Y.L.J., M.N., A.A., F.F. and P.J.P. performed bioinformatics analyses. M.H. and U.E. conducted the CiA assay with support from O.B. D.J.W. assisted with the SONO-seq experiments and H.Y.C. helped with the ATAC-seq assay. J.M., M.H. and M.Z. assisted with western blot and chromatin studies. D.T. and J.R. conducted ChIP experiments and library construction. M.S. and S.E.V. provided secondary Oct4\u2013tdTomato MEFs. J.Z. and S.W.L. provided the arrayed library. J.Z. and P.R. designed the extended chromatin library. M.F., J.J. and B.H. generated lentiviral vectors and RNAi reagents. J.M.P. and G.A. provided intellectual support and mentoring. K.H., S.C., J.Z. and U.E. wrote the paper with input from all co-authors. \n\nThe authors declare no competing financial interests. \n\nAll SONO-seq, ATAC-seq, ChIP-seq, RNA-seq and microarray data have been deposited in the Gene Expression Omnibus database under accession number GSE66534.\n\nAccepted Version - nihms-726948.pdf
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", "abstract": "Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.", "date": "2015-12-10", "date_type": "published", "publication": "Nature", "volume": "528", "number": "7581", "publisher": "Nature Publishing Group", "pagerange": "218-224", "id_number": "CaltechAUTHORS:20160105-101557021", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160105-101557021", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Defense", "grant_number": "CA 120212" }, { "agency": "NIH", "grant_number": "P50-HG007735" }, { "agency": "IMBA" }, { "agency": "FWF Der Wissenschaftsfonds" }, { "agency": "National Cancer Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "European Research Council (ERC)", "grant_number": "341036" }, { "agency": "Innovator Award/Era of Hope Award", "grant_number": "W81XWH-12-1-0093" }, { "agency": "European Research Council (ERC)", "grant_number": "336860" }, { "agency": "Boehringer Ingelheim" }, { "agency": "MGH" }, { "agency": "NIH", "grant_number": "R01 HD058013-06" }, { "agency": "Gerald and Darlene Jordan Chair in Regenerative Medicine" } ] }, "doi": "10.1038/nature15749", "pmcid": "PMC4866648", "primary_object": { "basename": "nature15749-sf8.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf8.jpg" }, "related_objects": [ { "basename": "nature15749-sf9.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf9.jpg" }, { "basename": "nature15749-s1.pdf", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s1.pdf" }, { "basename": "nature15749-s4.xlsx", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s4.xlsx" }, { "basename": "nature15749-s5.xlsx", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s5.xlsx" }, { "basename": "nature15749-sf4.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf4.jpg" }, { "basename": "nature15749-sf7.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf7.jpg" }, { "basename": "nature15749-sf6.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf6.jpg" }, { "basename": "nature15749-s6.xlsx", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s6.xlsx" }, { "basename": "nature15749-sf1.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf1.jpg" }, { "basename": "nature15749-sf2.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf2.jpg" }, { "basename": "nature15749-sf3.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf3.jpg" }, { "basename": "nature15749-sf5.jpg", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-sf5.jpg" }, { "basename": "nature15749-s2.xlsx", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s2.xlsx" }, { "basename": "nature15749-s3.xlsx", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nature15749-s3.xlsx" }, { "basename": "nihms-726948.pdf", "url": "https://authors.library.caltech.edu/records/jjax6-csn88/files/nihms-726948.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Cheloufi, Sihem; Ninova, Maria; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/btnyt-79371", "eprint_id": 59819, "eprint_status": "archive", "datestamp": "2023-08-20 07:52:35", "lastmod": "2023-10-23 22:45:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Manakov-Sergei-A", "name": { "family": "Manakov", "given": "Sergei A." } }, { "id": "Pezic-Dubravka", "name": { "family": "Pezic", "given": "Dubravka" }, "orcid": "0000-0002-9833-8469" }, { "id": "Marinov-Georgi-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Pastor-William-A", "name": { "family": "Pastor", "given": "William A." } }, { "id": "Sachidanandam-Ravi", "name": { "family": "Sachidanandam", "given": "Ravi" }, "orcid": "0000-0001-9844-4459" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "MIWI2 and MILI Have Differential Effects on piRNA Biogenesis and DNA Methylation", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). \n\nReceived: May 14, 2015; revised: July 2, 2015; accepted: July 16, 2015; published: August 13, 2015.\n\nWe thank Katalin Fejes T\u00f3th and members of the Aravin lab for helpful discussion and comments on the manuscript. We thank Alyssa Maskell (Caltech) for assistance with mouse work. We thank Igor Antoshechkin (Caltech) for help with RNA-seq and Maria Ninova for help with genome annotation. This work was supported by grants from the NIH (R00 HD057233 and DP2 OD007371A) and by the Searle Scholar Award and Packard Fellowship (to A.A.A.).\n\nAuthor Contributions: \nS.A.M., D.P., and A.A.A. designed the experiments. D.P. performed the experiments,\nS.A.M. performed computational analysis of all deep-sequencing\ndata, and G.K.M. performed ping-pong analysis. R.S. created bioinformatics\ntools for small RNA analysis. W.A.P. cloned and sequenced RNA-seq libraries\nfrom Mili mutant. S.A.M., D.P., and A.A.A. interpreted the data and wrote the\nmanuscript.\n\nPublished - 1-s2.0-S2211124715007962-main.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.pdf
", "abstract": "In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use Piwi-interacting RNA (piRNA) guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here, we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2 deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 is, suggesting that the proteins have independent roles in establishing DNA methylation patterns.", "date": "2015-08-25", "date_type": "published", "publication": "Cell Reports", "volume": "12", "number": "8", "publisher": "Cell Press", "pagerange": "1234-1243", "id_number": "CaltechAUTHORS:20150821-154811940", "issn": "2211-1247", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150821-154811940", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1016/j.celrep.2015.07.036", "pmcid": "PMC4554733", "primary_object": { "basename": "1-s2.0-S2211124715007962-main.pdf", "url": "https://authors.library.caltech.edu/records/btnyt-79371/files/1-s2.0-S2211124715007962-main.pdf" }, "related_objects": [ { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/btnyt-79371/files/mmc1.pdf" }, { "basename": "mmc2.pdf", "url": "https://authors.library.caltech.edu/records/btnyt-79371/files/mmc2.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Manakov, Sergei A.; Pezic, Dubravka; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4w9ed-6g304", "eprint_id": 59966, "eprint_status": "archive", "datestamp": "2023-08-20 07:49:23", "lastmod": "2023-10-23 23:26:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Webster-Alexandre", "name": { "family": "Webster", "given": "Alexandre" }, "orcid": "0000-0002-1416-5872" }, { "id": "Li-Sisi", "name": { "family": "Li", "given": "Sisi" }, "orcid": "0000-0002-7290-8128" }, { "id": "Hur-Junho-K", "name": { "family": "Hur", "given": "Junho K." }, "orcid": "0000-0003-3794-1149" }, { "id": "Wachsmuth-Maite", "name": { "family": "Wachsmuth", "given": "Malte" } }, { "id": "Bois-J-S", "name": { "family": "Bois", "given": "Justin S." }, "orcid": "0000-0001-7137-8746" }, { "id": "Perkins-Edward-M", "name": { "family": "Perkins", "given": "Edward M." } }, { "id": "Patel-Dinshaw-J", "name": { "family": "Patel", "given": "Dinshaw J." }, "orcid": "0000-0002-9779-7778" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Aub and Ago3 Are Recruited to Nuage through Two Mechanisms to Form a Ping-Pong Complex Assembled by Krimper", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Elsevier Inc. \n\nReceived: March 23, 2015; Revised: June 26, 2015; Accepted: July 20, 2015; Published: August 20, 2015. \n\nWe thank Katalin Fejes Toth and members of the Aravin and Fejes Toth labs for discussion and critical review of this manuscript. The authors would like to thank Andres Collazo and the Beckman Imaging Facility at the California Institute of Technology and Peter Rapp for assistance in developing our FRAP protocol, Georgi Marinov for assistance with piRNA analysis, and Igor Antoshechkin of the Millard and Muriel Jacobs Genetics and Genomics Laboratory. We are grateful to Julius Brennecke, Phillip Zamore, Zhao Zhang, and Toshie Kai, for fly stocks and other reagents. This work was supported by grants from the National Institutes of Health (R01 GM097363 and DP2 OD007371A) and by the Searle Scholar and the Packard Fellowship Awards to A.A.A.\n\nAccepted Version - nihms710553.pdf
Supplemental Material - mmc1.pdf
", "abstract": "In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3), localize to perinuclear \"nuage\" granules and use guide piRNAs to target and destroy transposable element transcripts. We find that Aub and Ago3 are recruited to nuage by two different mechanisms. Aub requires a piRNA guide for nuage recruitment, indicating that its localization depends on recognition of RNA targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on interaction with Krimper, a stable component of nuage that is able to aggregate in the absence of other nuage proteins. We show that Krimper interacts directly with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact with Krimper, but they are dispensable for Ago3 to bind Krimper. Our study reveals a multi-step process responsible for the assembly and function of nuage complexes in piRNA-guided transposon repression.", "date": "2015-08-20", "date_type": "published", "publication": "Molecular Cell", "volume": "59", "number": "4", "publisher": "Cell Press", "pagerange": "564-575", "id_number": "CaltechAUTHORS:20150828-150039771", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150828-150039771", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholar" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1016/j.molcel.2015.07.017", "pmcid": "PMC4545750", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/4w9ed-6g304/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms710553.pdf", "url": "https://authors.library.caltech.edu/records/4w9ed-6g304/files/nihms710553.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Webster, Alexandre; Li, Sisi; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4g5pf-zxf66", "eprint_id": 56169, "eprint_status": "archive", "datestamp": "2023-08-20 05:30:56", "lastmod": "2023-10-20 23:44:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Marinov-Georgi-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Wang-Jie", "name": { "family": "Wang", "given": "Jie" } }, { "id": "Handler-Dominik", "name": { "family": "Handler", "given": "Dominik" } }, { "id": "Wold-B-J", "name": { "family": "Wold", "given": "Barbara J." }, "orcid": "0000-0003-3235-8130" }, { "id": "Weng-Zhiping", "name": { "family": "Weng", "given": "Zhiping" } }, { "id": "Hannon-Gregory-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Zamore-Phillip-D", "name": { "family": "Zamore", "given": "Phillip D." } }, { "id": "Brennecke-Julius", "name": { "family": "Brennecke", "given": "Julius" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" } ] }, "title": "Pitfalls of Mapping High-Throughput Sequencing Data to Repetitive Sequences: Piwi's Genomic Targets Still Not Identified", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Elsevier Inc.\n\nReceived: July 17, 2014; Revised: December 18, 2014; Accepted: January 14, 2015; Published: March 23, 2015.\n\nG.K.M., J.W., and D.H. performed the computational analyses; all authors analyzed the data and wrote the manuscript. We thank Haifan Lin for kindly sharing the detailed computational pipeline underlying the analyses in Huang et al. (2013).\n\nAccepted Version - nihms703574.pdf
Supplemental Material - mmc1.pdf
", "abstract": "Huang et al. (2013) recently reported that chromatin immunoprecipitation sequencing (ChIP-seq) reveals the genome-wide sites of occupancy by Piwi, a piRNA-guided Argonaute protein central to transposon silencing in Drosophila. Their study also reported that loss of Piwi causes widespread rewiring of transcriptional patterns, as evidenced by changes in RNA polymerase II occupancy across the genome. Here we reanalyze their data and report that the underlying deep-sequencing dataset does not support the authors' genome-wide conclusions.", "date": "2015-03-23", "date_type": "published", "publication": "Developmental Cell", "volume": "32", "number": "6", "publisher": "Cell Press", "pagerange": "765-771", "id_number": "CaltechAUTHORS:20150327-092616999", "issn": "1534-5807", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150327-092616999", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.devcel.2015.01.013", "pmcid": "PMC4494788", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/4g5pf-zxf66/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms703574.pdf", "url": "https://authors.library.caltech.edu/records/4g5pf-zxf66/files/nihms703574.pdf" } ], "resource_type": "article", "pub_year": "2015", "author_list": "Marinov, Georgi K.; Wang, Jie; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r9rzh-6js56", "eprint_id": 73234, "eprint_status": "archive", "datestamp": "2023-08-22 15:06:00", "lastmod": "2023-10-24 15:08:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Non-coding RNAs in Transcriptional Regulation", "ispublished": "pub", "full_text_status": "public", "keywords": "Small RNA; lncRNA; Argonaute; PIWI; TGS; RdDM", "note": "\u00a9 2015 Springer International Publishing AG. \n\nPublished online: 17 February 2015. \n\nWe thank members of the Aravin lab and particularly Alexandre Webster for discussion and comments. The work in Aravin laboratory is supported by grants from the National Institutes of Health (R01 GM097363 and DP2 OD007371A) and by the Damon Runyon-Rachleff, the Searle Scholar, and the Packard Fellowship Awards to A.A.A. \n\nCompliance with Ethics Guidelines. \n\nYung-Chia Ariel Chen and Alexei A. Aravin declare that they have no conflict of interest. \n\nHuman and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors.\n\nAccepted Version - nihms664932.pdf
", "abstract": "Transcriptional gene silencing guided by small RNAs is a process conserved from protozoa to mammals. Small RNAs loaded into Argonaute family proteins direct repressive histone modifications or DNA cytosine methylation to homologous regions of the genome. Small RNA-mediated transcriptional silencing is required for many biological processes, including repression of transposable elements, maintaining the genome stability/integrity, and epigenetic inheritance of gene expression. Here, we will summarize the current knowledge about small RNA biogenesis and mechanisms of transcriptional regulation in plants, Drosophila, Caenorhabditis elegans, and mice. Furthermore, a rapidly growing number of long non-coding RNAs (lncRNAs) have been implicated as important players in transcription regulation. We will discuss current models for long non-coding RNA-mediated gene regulation.", "date": "2015-03", "date_type": "published", "publication": "Current Molecular Biology Reports", "volume": "1", "number": "1", "publisher": "Springer", "pagerange": "10-18", "id_number": "CaltechAUTHORS:20170104-154530088", "issn": "2198-6428", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170104-154530088", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Damon Runyon Cancer Research Foundation" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1007/s40610-015-0002-6", "pmcid": "PMC4479201", "primary_object": { "basename": "nihms664932.pdf", "url": "https://authors.library.caltech.edu/records/r9rzh-6js56/files/nihms664932.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Chen, Yung-Chia Ariel and Aravin, Alexei A." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/nve1g-k1t64", "eprint_id": 54464, "eprint_status": "archive", "datestamp": "2023-08-22 14:22:33", "lastmod": "2023-10-23 18:00:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pastor-William-A", "name": { "family": "Pastor", "given": "William A." } }, { "id": "Stroud-Hume", "name": { "family": "Stroud", "given": "Hume" }, "orcid": "0000-0002-2865-5258" }, { "id": "Nee-Kevin", "name": { "family": "Nee", "given": "Kevin" }, "orcid": "0000-0002-9892-0598" }, { "id": "Liu-Wanlu", "name": { "family": "Liu", "given": "Wanlu" } }, { "id": "Pezic-Dubravka", "name": { "family": "Pezic", "given": "Dubravka" }, "orcid": "0000-0002-9833-8469" }, { "id": "Manakov-Sergei-A", "name": { "family": "Manakov", "given": "Sergei A." } }, { "id": "Lee-Serena-A", "name": { "family": "Lee", "given": "Serena A." } }, { "id": "Moissiard-Guillaume", "name": { "family": "Moissiard", "given": "Guillaume" }, "orcid": "0000-0002-9532-6876" }, { "id": "Zamudio-Natasha", "name": { "family": "Zamudio", "given": "Natasha" }, "orcid": "0000-0002-2532-5931" }, { "id": "Bourc'his-D\u00e9borah", "name": { "family": "Bourc'his", "given": "D\u00e9borah" }, "orcid": "0000-0001-9499-7291" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Clark-Amander-T", "name": { "family": "Clark", "given": "Amander T." }, "orcid": "0000-0003-2483-3982" }, { "id": "Jacobsen-Steven-E", "name": { "family": "Jacobsen", "given": "Steven E." }, "orcid": "0000-0001-9483-138X" } ] }, "title": "MORC1 represses transposable elements in the mouse male germline", "ispublished": "pub", "full_text_status": "public", "keywords": "Biological sciences; Cell biology; Molecular biology", "note": "\u00a9 2014 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/\n\nReceived 12 September 2014; Accepted 7 November 2014; Published 12 December 2014.\n\nWe acknowledge the UCLA BSCRC Flow Cytometry core for flow and FACS assistance, and the UCLA BSCRC High Throughput Sequencing Core. Bryan Cullen provided anti-IAP Gag antibody and Alexander Bortvin provided anti-LINE ORF1p antibody. Jiamu Du and Dinshaw Patel provided recombinant MORC1 coiled-coil domain to raise antibody. W.A.P. is supported by the Jane Coffin Childs Memorial Fund for Medical Research. H.S. is an HHMI Fellow of the Damon Runyon Cancer Research Foundation (DRG-2194-14). W.L. is supported by a grant from the Chinese Scholar Council. This work was supported by grants from the NIH (R01 HD058047 and DP2 OD007371A), a Research Award from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the Nogradi Fund, the Searle Scholar and the Packard Fellowship Awards, and an ANR grant (\"TranspoFertil\"). S.E.J. is an investigator of the Howard Hughes Medical Institute.\n\nPublished - ncomms6795.pdf
Supplemental Material - ncomms6795-s1.pdf
Supplemental Material - ncomms6795-s2.xlsx
Supplemental Material - ncomms6795-s3.xlsx
Supplemental Material - ncomms6795-s4.xlsx
Supplemental Material - ncomms6795-s5.xlsx
Supplemental Material - ncomms6795-s6.xlsx
Erratum - ncomms8604.pdf
", "abstract": "The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. MORC1-deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation.", "date": "2014-12", "date_type": "published", "publication": "Nature Communications", "volume": "5", "number": "12", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 5795", "id_number": "CaltechAUTHORS:20150205-164216193", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150205-164216193", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" }, { "agency": "Damon Runyon Cancer Research Foundation", "grant_number": "DRG-2194-14" }, { "agency": "Chinese Scholar Council" }, { "agency": "NIH", "grant_number": "R01 HD058047" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research" }, { "agency": "Nogradi Fund" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Agence Nationale pour la Recherche (ANR)" } ] }, "doi": "10.1038/ncomms6795", "pmcid": "PMC4268658", "primary_object": { "basename": "ncomms6795-s4.xlsx", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s4.xlsx" }, "related_objects": [ { "basename": "ncomms6795-s5.xlsx", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s5.xlsx" }, { "basename": "ncomms6795-s6.xlsx", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s6.xlsx" }, { "basename": "ncomms6795.pdf", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795.pdf" }, { "basename": "ncomms8604.pdf", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms8604.pdf" }, { "basename": "ncomms6795-s1.pdf", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s1.pdf" }, { "basename": "ncomms6795-s2.xlsx", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s2.xlsx" }, { "basename": "ncomms6795-s3.xlsx", "url": "https://authors.library.caltech.edu/records/nve1g-k1t64/files/ncomms6795-s3.xlsx" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Pastor, William A.; Stroud, Hume; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/p2krk-dpt45", "eprint_id": 49643, "eprint_status": "archive", "datestamp": "2023-08-20 03:01:15", "lastmod": "2023-10-17 21:36:17", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Thomas-A", "name": { "family": "Le Thomas", "given": "Adrien" } }, { "id": "Marinov-G-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "A Transgenerational Process Defines piRNA Biogenesis in Drosophila virilis", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). \n\nReceived: April 6, 2014. Revised: May 22, 2014. Accepted: August 6, 2014. Published: September 4, 2014.\nWe thank Katalin Fejes Toth and members of the Aravin lab for discussion. This work was supported by grants from the NIH (R01 GM097363 and DP2 OD007371A) and by the Damon Runyon-Rachleff, the Searle Scholar, and the Packard Fellowship Awards to A.A.A.\n\nPublished - 1-s2.0-S2211124714006767-main.pdf
Accepted Version - nihms623129.pdf
Supplemental Material - mmc1.pdf
", "abstract": "Piwi-interacting (pi)RNAs repress diverse transposable elements in germ cells of Metazoa and are essential for fertility in both invertebrates and vertebrates. The precursors of piRNAs are transcribed from distinct genomic regions, the so-called piRNA clusters; however, how piRNA clusters are differentiated from the rest of the genome is not known. To address this question, we studied piRNA biogenesis in two D. virilis strains that show differential ability to generate piRNAs from several genomic regions. We found that active piRNA biogenesis correlates with high levels of histone 3 lysine 9 trimethylation (H3K9me3) over genomic regions that give rise to piRNAs. Furthermore, piRNA biogenesis in the progeny requires the transgenerational inheritance of an epigenetic signal, presumably in the form of homologous piRNAs that are generated in the maternal germline and deposited into the oocyte. The inherited piRNAs enhance piRNA biogenesis through the installment of H3K9me3 on piRNA clusters.", "date": "2014-09-25", "date_type": "published", "publication": "Cell Reports", "volume": "8", "number": "6", "publisher": "Elsevier", "pagerange": "1617-1623", "id_number": "CaltechAUTHORS:20140912-091626291", "issn": "2211-1247", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140912-091626291", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Damon Runyon-Rachleff Award" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1016/j.celrep.2014.08.013", "pmcid": "PMC5054749", "primary_object": { "basename": "1-s2.0-S2211124714006767-main.pdf", "url": "https://authors.library.caltech.edu/records/p2krk-dpt45/files/1-s2.0-S2211124714006767-main.pdf" }, "related_objects": [ { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/p2krk-dpt45/files/mmc1.pdf" }, { "basename": "nihms623129.pdf", "url": "https://authors.library.caltech.edu/records/p2krk-dpt45/files/nihms623129.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Le Thomas, Adrien; Marinov, Georgi K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cv8jf-3m314", "eprint_id": 48167, "eprint_status": "archive", "datestamp": "2023-08-22 13:20:48", "lastmod": "2023-10-17 16:33:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Thomas-Adrien", "name": { "family": "Le Thomas", "given": "Adrien" } }, { "id": "Stuwe-Evelyn", "name": { "family": "Stuwe", "given": "Evelyn" } }, { "id": "Li-Sisi", "name": { "family": "Li", "given": "Sisi" } }, { "id": "Du-Jiamu", "name": { "family": "Du", "given": "Jiamu" } }, { "id": "Marinov-Georgi-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Rozhkov-Nikolay-V", "name": { "family": "Rozhkov", "given": "Nikolay V." } }, { "id": "Chen-Yung-Chia-Ariel", "name": { "family": "Chen", "given": "Yung-Chia Ariel" } }, { "id": "Luo-Yucheng", "name": { "family": "Luo", "given": "Yucheng" } }, { "id": "Sachidanandam-Ravi", "name": { "family": "Sachidanandam", "given": "Ravi" }, "orcid": "0000-0001-9844-4459" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Patel-Dinshaw-J", "name": { "family": "Patel", "given": "Dinshaw" }, "orcid": "0000-0002-9779-7778" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing", "ispublished": "pub", "full_text_status": "public", "keywords": "H3K9me3; epigenetics; piRNA", "note": "\u00a9 2014 Le Thomas et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml).\nAfter six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.\n\nReceived May 14, 2014; revised version accepted July 9, 2014.\n\nWe thank members of the Aravin laboratory for discussion.We are grateful to the staff at beamline 24-ID-E at the Argonne National Laboratory and beamline X29A at the Brookhaven National Laboratory for support in diffraction data collection. E.S. is supported by a Ph.D. fellowship of the Boehringer Ingelheim Fonds. This work was supported by grants from the National Institutes of Health (R00 HD057233, R01 GM097363, and DP2 OD007371A) and by the Searle Scholar and the Packard Fellowship Awards to A.A.A., and by funds from the Abby Rockefeller Mauze Trust, Maloris Foundation, and Starr Foundation to D.P.\n\nPublished - Genes_Dev.-2014-Le_Thomas-1667-80.pdf
Supplemental Material - Supplemental_Figure_Legends.docx
Supplemental Material - Supplemental_Figures.pdf
Supplemental Material - Supplemental_Tables.docx
", "abstract": "Small noncoding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that transgenerationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the histone 3 Lys9 trimethylation (H3K9me3) mark on genomic piRNA cluster sequences. The heterochromatin protein 1 (HP1) homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that transgenerationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels: by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors.", "date": "2014-08-01", "date_type": "published", "publication": "Genes and Development", "volume": "28", "number": "15", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "1667-1680", "id_number": "CaltechAUTHORS:20140807-085550951", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140807-085550951", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Boehringer Ingelheim Fonds" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Abby Rockefeller Mauze Trust" }, { "agency": "Maloris Foundation" }, { "agency": "Starr Foundation" } ] }, "doi": "10.1101/gad.245514.114", "pmcid": "PMC4117942", "primary_object": { "basename": "Genes_Dev.-2014-Le_Thomas-1667-80.pdf", "url": "https://authors.library.caltech.edu/records/cv8jf-3m314/files/Genes_Dev.-2014-Le_Thomas-1667-80.pdf" }, "related_objects": [ { "basename": "Supplemental_Figure_Legends.docx", "url": "https://authors.library.caltech.edu/records/cv8jf-3m314/files/Supplemental_Figure_Legends.docx" }, { "basename": "Supplemental_Figures.pdf", "url": "https://authors.library.caltech.edu/records/cv8jf-3m314/files/Supplemental_Figures.pdf" }, { "basename": "Supplemental_Tables.docx", "url": "https://authors.library.caltech.edu/records/cv8jf-3m314/files/Supplemental_Tables.docx" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Le Thomas, Adrien; Stuwe, Evelyn; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2eptk-z9w94", "eprint_id": 48580, "eprint_status": "archive", "datestamp": "2023-08-22 13:12:12", "lastmod": "2023-10-17 19:27:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Molaro-Antoine", "name": { "family": "Molaro", "given": "Antoine" } }, { "id": "Falciatori-Ilaria", "name": { "family": "Falciatori", "given": "Ilaria" } }, { "id": "Hodges-Emily", "name": { "family": "Hodges", "given": "Emily" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Marran-Krista", "name": { "family": "Marran", "given": "Krista" } }, { "id": "Rafii-Shahin", "name": { "family": "Rafii", "given": "Shahin" } }, { "id": "McCombie-W-Richard", "name": { "family": "McCombie", "given": "W. Richard" } }, { "id": "Smith-Andrew-D", "name": { "family": "Smith", "given": "Andrew D." } }, { "id": "Hannon-Gregory-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "Two waves of de novo methylation during mouse germ cell development", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA methylation; piRNA; retrotransposon; germ cells; LINE; LTR", "note": "\u00a9 2014 Molaro et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.\n\nReceived April 25, 2014; revised version accepted June 16,\n2014.\n\nWe acknowledge members of the Hannon and Smith laboratories for advice on experimental design, and especially Assaf Gordon, the Cold Spring Harbor Laboratory Bioinformatics Shared Resource, Emily Lee, and Maria Mosquera for technical help. We acknowledge the Cold Spring Harbor Laboratory animal facility for help with mouse handling. This research was supported through a National Institutes of Health (NIH) stimulus grant (no. 5RC2HD064459-01) and R37GM062534 to G.J.H., and NIH R01 grant HG006015 to A.D.S. Raw sequencing data were deposited for download on Sequence Read Archive under accession numbers SRP037785, SRP037807, and SRP037987.\n\nPublished - Genes_Dev.-2014-Molaro-1544-9.pdf
Supplemental Material - SuppMaterial_REV.pdf
", "abstract": "During development, mammalian germ cells reprogram their epigenomes via a genome-wide erasure and de novo rewriting of DNA methylation marks. We know little of how methylation patterns are specifically determined. The piRNA pathway is thought to target the bulk of retrotransposon methylation. Here we show that most retrotransposon sequences are modified by default de novo methylation. However, potentially active retrotransposon copies evade this initial wave, likely mimicking features of protein-coding genes. These elements remain transcriptionally active and become targets of piRNA-mediated methylation. Thus, we posit that these two waves play essential roles in resetting germ cell epigenomes at each generation.", "date": "2014-07-15", "date_type": "published", "publication": "Genes and Development", "volume": "28", "number": "14", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "1544-1549", "id_number": "CaltechAUTHORS:20140814-154014567", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140814-154014567", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "5RC2HD064459-01" }, { "agency": "NIH", "grant_number": "R37GM062534" }, { "agency": "NIH", "grant_number": "R01 HG006015" } ] }, "doi": "10.1101/gad.244350.114", "pmcid": "PMC4102761", "primary_object": { "basename": "SuppMaterial_REV.pdf", "url": "https://authors.library.caltech.edu/records/2eptk-z9w94/files/SuppMaterial_REV.pdf" }, "related_objects": [ { "basename": "Genes_Dev.-2014-Molaro-1544-9.pdf", "url": "https://authors.library.caltech.edu/records/2eptk-z9w94/files/Genes_Dev.-2014-Molaro-1544-9.pdf" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Molaro, Antoine; Falciatori, Ilaria; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b4w1e-1an77", "eprint_id": 46429, "eprint_status": "archive", "datestamp": "2023-08-22 13:08:17", "lastmod": "2023-10-26 19:44:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Pezic-Dubravka", "name": { "family": "Pezic", "given": "Dubravka" }, "orcid": "0000-0002-9833-8469" }, { "id": "Manakov-Sergei-A", "name": { "family": "Manakov", "given": "Sergei A." } }, { "id": "Sachidanandam-Ravi", "name": { "family": "Sachidanandam", "given": "Ravi" }, "orcid": "0000-0001-9844-4459" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells", "ispublished": "pub", "full_text_status": "public", "keywords": "H3K9me3; piRNA; transposon", "note": "\u00a9 2014 Pezic et al.; Published by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml).\nAfter six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.\n\nPublished online June 17, 2014 in advance of the print journal; received March 3, 2014; revised version accepted May 28, 2014.\n\nWe thank Katalin Fejes T\u00f3th and members of the Aravin\nlaboratory for helpful discussion and comments on the manuscript. We thank Rochelle Diamond and Diana Perez (California Institute of Technology) for invaluable help with cell sorting. We thank Alyssa Maskell (California Institute of Technology) for assistance with mouse work.We thank the Baltimore laboratory (California Institute of Technology) for lending us their magnetic cell-sorting equipment. We thank Sailakshmi Subramanian (Mount Sinai), Stijn van Dongen (EMBL-EBI), Georgi Marinov, Henry Amrhein, and Diane Trout (all California Institute of Technology) for help with bioinformatic and statistical analysis, and Igor Antoshechkin (California Institute of Technology) for help with RNA-seq. This work was supported by grants from the National Institutes of Health (R00 HD057233, R01 GM097363, and DP2 OD007371A), the Searle Scholar Award, and the Packard Fellowship to A.A.A.\n\nPublished - 1410.full.pdf
Supplemental Material - Supplemental_Figures_and_Legends.docx
", "abstract": "Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments.", "date": "2014-07-01", "date_type": "published", "publication": "Genes and Development", "volume": "28", "number": "13", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "1410-1418", "id_number": "CaltechAUTHORS:20140623-092336462", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140623-092336462", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1101/gad.240895.114", "pmcid": "PMC4083086", "primary_object": { "basename": "1410.full.pdf", "url": "https://authors.library.caltech.edu/records/b4w1e-1an77/files/1410.full.pdf" }, "related_objects": [ { "basename": "Supplemental_Figures_and_Legends.docx", "url": "https://authors.library.caltech.edu/records/b4w1e-1an77/files/Supplemental_Figures_and_Legends.docx" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Pezic, Dubravka; Manakov, Sergei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/15rma-98v78", "eprint_id": 45862, "eprint_status": "archive", "datestamp": "2023-08-20 01:06:08", "lastmod": "2023-10-26 18:30:19", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hur-J-K", "name": { "family": "Hur", "given": "Junho K." } }, { "id": "Olovnikov-I", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Prokaryotic Argonautes defend genomes against invasive DNA", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Elsevier Ltd.\n\nAvailable online 13 May 2014. \n\nWe thank members of the Aravin lab for discussion and Alexandre Webster for critical reading of the manuscript. Research in Aravin lab is supported by grants from the National Institutes of Health (HD057233, GM097363, and OD007371A) and by the Searle Scholar and the Packard Fellowship Awards.\n\nAccepted Version - nihms591653.pdf
", "abstract": "Argonaute proteins are central players in small RNAmediated\nsilencing mechanisms such as RNA interference (RNAi), microRNA repression and piRNA-mediated transposon silencing. In eukaryotes, Argonautes bind small RNAs that guide them to RNA targets in order to regulate gene expression and repress invasive genomic elements. Although Argonaute proteins are conserved in all life forms from bacteria to eukaryotes, until now studies have focused on the biological functions of eukaryotic Argonautes. Here we highlight two recent studies that discover the functions of prokaryotic Argonautes in defence against exogenous DNA.", "date": "2014-06", "date_type": "published", "publication": "Trends in Biochemical Sciences", "volume": "39", "number": "6", "publisher": "Elsevier", "pagerange": "257-259", "id_number": "CaltechAUTHORS:20140521-090032542", "issn": "0968-0004", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140521-090032542", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "HD057233" }, { "agency": "NIH", "grant_number": "GM097363" }, { "agency": "NIH", "grant_number": "OD007371A" }, { "agency": "Searle Scholar Award" }, { "agency": "Packard Fellowship Award" } ] }, "doi": "10.1016/j.tibs.2014.04.006", "pmcid": "PMC4041519", "primary_object": { "basename": "nihms591653.pdf", "url": "https://authors.library.caltech.edu/records/15rma-98v78/files/nihms591653.pdf" }, "resource_type": "article", "pub_year": "2014", "author_list": "Hur, Junho K.; Olovnikov, Ivan; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kfdcd-r9h45", "eprint_id": 45179, "eprint_status": "archive", "datestamp": "2023-08-22 11:54:19", "lastmod": "2023-10-26 17:37:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Stuwe-E", "name": { "family": "Stuwe", "given": "Evelyn" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Small but sturdy: small RNAs in cellular memory and epigenetics", "ispublished": "pub", "full_text_status": "public", "keywords": "Argonautes; cellular memory; epigenetics; piRNA", "note": "\u00a9 2014 Stuwe et al. Published by Cold Spring Harbor Laboratory Press. \n\nThis article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/. \n\nWe thank members of the Aravin laboratory for discussion. E.S. is supported by a Ph.D. fellowship of the Boehringer Ingelheim Fonds. Work on this topic in the Aravin laboratory is supported by grants from the National Institutes of Health (R00 HD057233, R01 GM097363, and DP2 OD007371A) and the Searle Scholar and the Packard Fellowship Awards.\n\nPublished - Genes_Dev.-2014-Stuwe-423-31.pdf
", "abstract": "Cells in multicellular organisms have distinct identities\ncharacterized by their profiles of expressed genes. Cell\nidentities can be stable over a long time and through\nmultiple cellular divisions but are also responsive to\nextracellular signals. Since the DNA sequence is identical\nin all cells, a \"cellular memory\" of expression profiles\nis achieved by what are defined as epigenetic mechanisms.\nTwo major molecular principles\u2014networks of\ntranscription factors and maintenance of cis-chromatin\nmodifications\u2014have been implicated in maintaining\ncellular memory. Here we describe recent studies demonstrating that short noncoding RNAs can also provide\nmolecular signals that define epigenetic states of cells.\nSmall RNAs can act independently or cooperate with\nchromatin modifications to achieve long-lasting effects\nnecessary for cellular memory and transgenerational\ninheritance.", "date": "2014-03-01", "date_type": "published", "publication": "Genes and Development", "volume": "28", "number": "5", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "421-431", "id_number": "CaltechAUTHORS:20140424-085844076", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140424-085844076", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Boehringer Ingelheim Fonds" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" } ] }, "doi": "10.1101/gad.236414.113", "pmcid": "PMC3950340", "primary_object": { "basename": "Genes_Dev.-2014-Stuwe-423-31.pdf", "url": "https://authors.library.caltech.edu/records/kfdcd-r9h45/files/Genes_Dev.-2014-Stuwe-423-31.pdf" }, "resource_type": "article", "pub_year": "2014", "author_list": "Stuwe, Evelyn; Fejes T\u00f3th, Katalin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/tnqmx-2kk53", "eprint_id": 43563, "eprint_status": "archive", "datestamp": "2023-08-19 23:13:01", "lastmod": "2023-10-25 23:40:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Thomas-A", "name": { "family": "Le Thomas", "given": "Adrien" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "To be or not to be a piRNA: genomic origin and processing of piRNAs", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Le Thomas et al.; licensee BioMed Central Ltd. The licensee has exclusive rights to distribute this article, in any medium, for 12 months following its publication. After this time, the article is available under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nPublished: 27 January 2014. \n\nWe thank Evelyn Stuwe for help with figure preparation and members of the Aravin laboratory for discussion. This work was supported by grants from the National Institutes of Health (R00 HD057233, R01 GM097363 and DP2 OD007371A), the Searle Scholar, the Packard Fellowship Awards and the Ellison Medical Foundation New Scholar Aging Award.\n\nPublished - LeThomas_2014.pdf
", "abstract": "Piwi-interacting RNAs (piRNAs) originate from genomic\nregions dubbed piRNA clusters. How cluster transcripts\nare selected for processing into piRNAs is not\nunderstood. We discuss evidence for the involvement\nof chromatin structure and maternally inherited\npiRNAs in determining their fate.", "date": "2014-01-27", "date_type": "published", "publication": "Genome Biology", "volume": "15", "number": "1", "publisher": "BioMed Central", "pagerange": "Art. No. 204", "id_number": "CaltechAUTHORS:20140130-080906919", "issn": "1465-6906", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140130-080906919", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholars Program" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Ellison Medical Foundation" } ] }, "doi": "10.1186/gb4154", "pmcid": "PMC4053809", "primary_object": { "basename": "LeThomas_2014.pdf", "url": "https://authors.library.caltech.edu/records/tnqmx-2kk53/files/LeThomas_2014.pdf" }, "resource_type": "article", "pub_year": "2014", "author_list": "Le Thomas, Adrien; Fejes T\u00f3th, Katalin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hkcs2-k3283", "eprint_id": 42373, "eprint_status": "archive", "datestamp": "2023-08-19 22:40:58", "lastmod": "2024-01-13 06:04:53", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olovnikov-I", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Le-Thomas-A", "name": { "family": "Le Thomas", "given": "Adrien" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "A Framework for piRNA Cluster Manipulation", "ispublished": "unpub", "full_text_status": "restricted", "keywords": "piRNA, piRNA cluster, BAC, Recombineering, phiC31", "note": "\u00a9 2014 Springer Science+Business Media, LLC. We thank members of the Aravin lab for helpful discussion and\ncomments on the manuscript. We are particularly thankful to\nAlexandre Webster for comments and editing. I.O. is a CEMI\n(Center for Environmental Microbiology Interactions) fellow at\nCaltech. This work was supported by grants from the National\nInstitutes of Health (R01 GM097363, R00 HD057233, and DP2\nOD007371A) and the Searle Scholar Award to A.A.A.", "abstract": "Piwi proteins and their small-RNA partners, piwi-interacting (pi)RNA, form a natural mechanism that\nprevents the deleterious activity of transposable elements in the germ line of metazoan species. The piRNA pathway relies on extended noncoding genomic regions, dubbed piRNA clusters, to produce long precursor transcripts that are subsequently processed into mature piRNAs. The large size and repetitive nature of piRNA clusters provide significant challenges for their dissection using common genetic tools. Here we describe an effective approach for manipulation of piRNA clusters using a combination of BAC recombineering\nin E. coli and phiC31-mediated transgenesis in Drosophila. Although the described approach is instrumental for manipulating piRNA clusters, it can also be implemented for other problems in functional genomics.", "date": "2014", "date_type": "published", "publisher": "Humana Press", "place_of_pub": "New York, NY", "pagerange": "47-58", "id_number": "CaltechAUTHORS:20131112-093205322", "isbn": "978-1-62703-693-1", "book_title": "PIWI-Interacting RNAs: Methods and Protocols", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20131112-093205322", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholar Award" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" } ] }, "contributors": { "items": [ { "id": "Siomi-M-C", "name": { "family": "Siomi", "given": "Mikiko C." } } ] }, "doi": "10.1007/978-1-62703-694-8_5", "resource_type": "book_section", "pub_year": "2014", "author_list": "Olovnikov, Ivan; Le Thomas, Adrien; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/4pnw6-x7v16", "eprint_id": 43887, "eprint_status": "archive", "datestamp": "2023-08-19 21:27:23", "lastmod": "2023-10-25 23:58:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olovnikov-I", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Chan-Ken", "name": { "family": "Chan", "given": "Ken" } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Newman-D-K", "name": { "family": "Newman", "given": "Diane K." }, "orcid": "0000-0003-1647-1918" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Bacterial Argonaute Samples the Transcriptome to Identify Foreign DNA", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2013 Elsevier Inc.\n\nReceived: July 18, 2013; Revised: August 8, 2013;\nAccepted: August 8, 2013; Published: September 12, 2013.\n\nWe thank Katalin Fejes T\u00f3th and members of the Aravin lab for helpful discussion and comments on the manuscript. We thank Chia-Hung Wu, Shannon Park, and Gargi Kulkarni from Dianne Newman's lab for guidance with bacterial experiments and Konstantin Piatkov for helpful suggestions. We thank Timothy Donohue (University of Wisconsin-Madison), Shulin Chen (WSU), Rebecca Parales (UC Davis), and Carlos R\u00edos-Vel\u00e1zquez (UPR-Mayag\u00fcez) for provided reagents and bacterial strains. We are grateful to Todd Lowe (UCSC) for providing access to the genome browser. We thank Sailakshmi Subramanian (Mount Sinai) and Georgi Marinov and Sergei Manakov (Caltech) for help with bioinformatic and statistical analysis, and Igor Antoshechkin (Caltech) for help with RNA sequencing. We thank Gregory Donaldson and Vishnu Manoranjan for assistance with experiments. I.O. is a Center for Environmental Microbiology Interactions (CEMI) fellow at Caltech. This work was supported by grants from the National Institutes of Health (R01 GM097363, R00 HD057233 and DP2 OD007371A) and the Searle Scholar Award (to A.A.A.). D.K.N. is an Investigator of the Howard Hughes Medical Institute.\nRNA-seq, small RNA, and small DNA data were deposited in the Gene Expression Omnibus database under accession number GSE49865.\n\nAccepted Version - nihms515739.pdf
Supplemental Material - mmc1.pdf
", "abstract": "Eukaryotic Argonautes bind small RNAs and use them as guides to find complementary RNA targets and induce gene silencing. Though homologs of eukaryotic Argonautes are present in many bacteria and archaea, their small RNA partners and functions are unknown. We found that the Argonaute of Rhodobacter sphaeroides (RsAgo) associates with 15\u201319 nt RNAs that correspond to the majority of transcripts. RsAgo also binds single-stranded 22\u201324 nt DNA molecules that are complementary to the small RNAs and enriched in sequences derived from exogenous plasmids as well as genome-encoded foreign nucleic acids such as transposons and phage genes. Expression of RsAgo in the heterologous E. coli system leads to formation of plasmid-derived small RNA and DNA and plasmid degradation. In a R. sphaeroides mutant lacking RsAgo, expression of plasmid-encoded genes is elevated. Our results indicate that RNAi-related processes found in eukaryotes are also conserved in bacteria and target foreign nucleic acids.", "date": "2013-09-12", "date_type": "published", "publication": "Molecular Cell", "volume": "51", "number": "5", "publisher": "Elsevier", "pagerange": "594-605", "id_number": "CaltechAUTHORS:20140220-100231898", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140220-100231898", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholar Award" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Division-of-Geological-and-Planetary-Sciences" } ] }, "doi": "10.1016/j.molcel.2013.08.014", "pmcid": "PMC3809076", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/4pnw6-x7v16/files/mmc1.pdf" }, "related_objects": [ { "basename": "nihms515739.pdf", "url": "https://authors.library.caltech.edu/records/4pnw6-x7v16/files/nihms515739.pdf" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Olovnikov, Ivan; Chan, Ken; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k8vb6-exp50", "eprint_id": 37810, "eprint_status": "archive", "datestamp": "2023-08-22 08:42:25", "lastmod": "2023-10-23 18:04:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Thomas-A", "name": { "family": "Le Thomas", "given": "Adrien" } }, { "id": "Rogers-A-K", "name": { "family": "Rogers", "given": "Alicia K." } }, { "id": "Webster-Alexandre", "name": { "family": "Webster", "given": "Alexandre" } }, { "id": "Marinov-G-K", "name": { "family": "Marinov", "given": "Georgi K." }, "orcid": "0000-0003-1822-7273" }, { "id": "Liao-Susan-E", "name": { "family": "Liao", "given": "Susan E." } }, { "id": "Perkins-E-M", "name": { "family": "Perkins", "given": "Edward M." } }, { "id": "Hur-Junho-K", "name": { "family": "Hur", "given": "Junho K." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes T\u00f3th", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" } ] }, "title": "Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state", "ispublished": "pub", "full_text_status": "public", "keywords": "piRNA; Piwi; chromatin; RNA polymerase II; transcription; transposon", "note": "\u00a9 2013 Cold Spring Harbor Laboratory Press.\n\nReceived November 8, 2012; revised version accepted January 14, 2013.\n\nWe are grateful to Evelyn Stuwe from the Aravin laboratory for purifying the GFP antibody; I. Antoshechkin of the Millard and Muriel Jacobs Genetics and Genomics Laboratory for sequencing; D. Trout, H. Amrhein, and S. Upchurch for computational assistance; the Bloomington Stock Center for fly stocks; and S. Hess, B. Graham, and M Sweredoski from the Proteome Exploration Laboratory at the Beckmann Institute, California Institute of Technology, for assistance with the mass spectrometry experiments. We thank members of the Aravin laboratory for critical comments on the manuscript. We thank Barbara Wold and members of the Wold laboratory for helpful discussions on ChIP protocols and analysis. A.K.R. and E.M.P. are supported by the Institutional Training Grant NIH/NRSA 5T32 GM07616,\nand E.M.P. is additionally supported by the Gordon Ross Medical Foundation. G.K.M. is supported by The Beckman Foundation, the Donald Bren Endowment, and NIH grant U54 HG004576. This work was supported by grants from the National Institutes of Health (R01 GM097363, R00 HD057233, and DP2 OD007371A to A.A.A.), the Searle Scholar Award (to A.A.A.), and the Ellison Medical Foundation New Scholar in Aging Award (to K.F.T.). \n\nFreely available online through the Genes & Development Open Access option.\n\nPublished - Genes_Dev.-2013-Le_Thomas-390-9.pdf
Supplemental Material - Supplemental_Material.pdf
Supplemental Material - Supplemental_Material.xlsx
", "abstract": "In the metazoan germline, piwi proteins and associated piwi-interacting RNAs (piRNAs) provide a defense system against the expression of transposable elements. In the cytoplasm, piRNA sequences guide piwi complexes to destroy complementary transposon transcripts by endonucleolytic cleavage. However, some piwi family members are nuclear, raising the possibility of alternative pathways for piRNA-mediated regulation of gene expression. We found that Drosophila Piwi is recruited to chromatin, colocalizing with RNA polymerase II (Pol II) on polytene chromosomes. Knockdown of Piwi in the germline increases expression of transposable elements that are targeted by piRNAs, whereas protein-coding genes remain largely unaffected. Derepression of transposons upon Piwi depletion correlates with increased occupancy of Pol II on their promoters. Expression of piRNAs that target a reporter construct results in a decrease in Pol II occupancy and an increase in repressive H3K9me3 marks and heterochromatin protein 1 (HP1) on the reporter locus. Our results indicate that Piwi identifies targets complementary to the associated piRNA and induces transcriptional repression by establishing a repressive chromatin state when correct targets are found.", "date": "2013-02-15", "date_type": "published", "publication": "Genes and Development", "volume": "27", "number": "4", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "390-399", "id_number": "CaltechAUTHORS:20130408-133337079", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20130408-133337079", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "5T32 GM07616" }, { "agency": "Gordon Ross Medical Foundation" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "Donald Bren Endowment" }, { "agency": "NIH", "grant_number": "U54 HG004576" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "Searle Scholar Award" }, { "agency": "Ellison Medical Foundation" } ] }, "doi": "10.1101/gad.209841.112", "pmcid": "PMC3589556", "primary_object": { "basename": "Genes_Dev.-2013-Le_Thomas-390-9.pdf", "url": "https://authors.library.caltech.edu/records/k8vb6-exp50/files/Genes_Dev.-2013-Le_Thomas-390-9.pdf" }, "related_objects": [ { "basename": "Supplemental_Material.pdf", "url": "https://authors.library.caltech.edu/records/k8vb6-exp50/files/Supplemental_Material.pdf" }, { "basename": "Supplemental_Material.xlsx", "url": "https://authors.library.caltech.edu/records/k8vb6-exp50/files/Supplemental_Material.xlsx" } ], "resource_type": "article", "pub_year": "2013", "author_list": "Le Thomas, Adrien; Rogers, Alicia K.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/26z9z-na010", "eprint_id": 95337, "eprint_status": "archive", "datestamp": "2023-08-22 07:40:47", "lastmod": "2023-10-20 19:09:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olenkina-O-M", "name": { "family": "Olenkina", "given": "O. M." } }, { "id": "Egorova-K-S", "name": { "family": "Egorova", "given": "K. S." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "N. M." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } }, { "id": "Olenina-L-V", "name": { "family": "Olenina", "given": "L. V." } } ] }, "title": "Mapping of cis-regulatory sites in the promoter of testis-specific Stellate genes of Drosophila melanogaster", "ispublished": "pub", "full_text_status": "restricted", "keywords": "promoter; spermatogenesis; Drosophila; Stellate genes; heterochromatin", "note": "\u00a9 2012 Pleiades Publishing, Ltd. Original Russian Text \u00a9 O. M. Olenkina, K. S. Egorova, A. A. Aravin, N. M. Naumova, V. A. Gvozdev, L. V. Olenina, 2012, published in Biokhimiya, 2012, Vol. 77, No. 11,\npp. 1536-1545. Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM12-191, October 21, 2012. \n\nReceived June 22, 2012; Revision received July 3, 2012. \n\nThis study was supported by the fundamental research program of the Presidium of the Russian Academy of Sciences \"Molecular and Cell Biology\" and by the Russian Foundation for Basic Research (grant Nos. 10-04-00535-a and 11-04-00017-a).", "abstract": "Tandem Stellate genes organized into two clusters in heterochromatin and euchromatin of the X-chromosome are part of the Ste-Su(Ste) genetic system required for maintenance of male fertility and reproduction of Drosophila melanogaster. Stellate genes encode a regulatory subunit of protein kinase CK2 and are the main targets of germline-specific piRNA-silencing; their derepression leads to appearance of protein crystals in spermatocytes, meiotic disturbances, and male sterility. A short promoter region of 134 bp appears to be sufficient for testis-specific transcription of Stellate, and it contains three closely located cis-regulatory elements called E-boxes. By using reporter analysis, we confirmed a strong functionality of the E-boxes in the Stellate promoter for in vivo transcription. Using selective mutagenesis, we have shown that the presence of the central E-box 2 is preferable to maintain a high-level testis-specific transcription of the reporter gene under the Stellate promoter. The Stellate promoter provides transcription even in heterochromatin, and corresponding mRNAs are translated with the generation of full-size protein products in case of disturbances in the piRNA-silencing process. We have also shown for the first time that the activity of the Stellate promoter is determined by chromatin context of the X-chromosome in male germinal cells, and it increases at about twofold when relocating in autosomes.", "date": "2012-11", "date_type": "published", "publication": "Biochemistry (Moscow)", "volume": "77", "number": "11", "publisher": "Pleiades Publishing Ltd", "pagerange": "1285-1293", "id_number": "CaltechAUTHORS:20190508-083305960", "issn": "0006-2979", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-083305960", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Presidium of the Russian Academy of Sciences" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "10-04-00535-a" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "11-04-00017-a" } ] }, "doi": "10.1134/s0006297912110077", "resource_type": "article", "pub_year": "2012", "author_list": "Olenkina, O. M.; Egorova, K. S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/k353a-n9p07", "eprint_id": 31973, "eprint_status": "archive", "datestamp": "2023-08-19 10:30:27", "lastmod": "2023-10-17 21:44:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olovnikov-I", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" } ] }, "title": "Small RNA in the nucleus: the RNA-chromatin ping-pong", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2012 Elsevier. \n\nAvailable online 19 February 2012. \n\nWe thank members of the Aravin Lab for helpful discussion and comments on the manuscript. This work is supported by grants from the National Institutes of Health (DP2 OD007371A, R00 HD057233 and R01GM097363) to A.A.A. and by the Ellison Medical Foundation grant to K.F.T.\n\nAccepted Version - nihms349994.pdf
", "abstract": "Eukaryotes use several classes of small RNA molecules to guide diverse protein machineries to target messenger RNA. The role of small RNA in post-transcriptional regulation of mRNA stability and translation is now well established. Small RNAs can also guide sequence-specific modification of chromatin structure and thus contribute to establishment and maintenance of distinct chromatin domains. In this review we summarize the model for the inter-dependent interaction between small RNA and chromatin that has emerged from studies on fission yeast and plants. We focus on recent results that link a distinct class of small RNAs, the piRNAs, to chromatin regulation in animals.", "date": "2012-04", "date_type": "published", "publication": "Current Opinion in Genetics and Development", "volume": "22", "number": "2", "publisher": "Elsevier", "pagerange": "164-171", "id_number": "CaltechAUTHORS:20120620-092051198", "issn": "1879-0380", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120620-092051198", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "R01 GM097363" }, { "agency": "Ellison Medical Foundation" } ] }, "doi": "10.1016/j.gde.2012.01.002", "pmcid": "PMC3345048", "primary_object": { "basename": "nihms349994.pdf", "url": "https://authors.library.caltech.edu/records/k353a-n9p07/files/nihms349994.pdf" }, "resource_type": "article", "pub_year": "2012", "author_list": "Olovnikov, Ivan; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/q2cdk-1k022", "eprint_id": 28982, "eprint_status": "archive", "datestamp": "2023-08-22 04:34:41", "lastmod": "2023-10-24 18:17:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Muerdter-F", "name": { "family": "Muerdter", "given": "Felix" } }, { "id": "Olovnikov-I", "name": { "family": "Olovnikov", "given": "Ivan" } }, { "id": "Molaro-A", "name": { "family": "Molaro", "given": "Antoine" } }, { "id": "Rozhkov-N-V", "name": { "family": "Rozhkov", "given": "Nikolay V." } }, { "id": "Czech-B", "name": { "family": "Czech", "given": "Benjamin" } }, { "id": "Gordon-A", "name": { "family": "Gordon", "given": "Azzaf" } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Production of artificial piRNAs in flies and mice", "ispublished": "pub", "full_text_status": "public", "keywords": "piwi; noncoding RNA; piRNA", "note": "\u00a9 2012 RNA Society. \nPublished by Cold Spring Harbor Laboratory Press.\nReceived August 8, 2011. Accepted September 26, 2011. Published in Advance November 17, 2011. We thank members of the Hannon and Aravin labs for helpful\ndiscussion and comments on the manuscript. We thank members \nof the McCombie lab (CSHL) and Igor Antoshechkin (Caltech)\nfor help with RNA sequencing. We thank Andres Canela (CSHL)\nfor technical assistance and Simon Knott (CSHL) and Alex Zahn (Caltech) for help with statistical analysis. Sang Yong Kim (CSHL) created the transgenic mice used in this study. F.M. was supported by the Volkswagen Foundation and B.C. by the Boehringer Ingelheim Fonds. This work was supported by grants from the National Institutes of Health (DP2 OD007371A and R00HD057233 to A.A.A.; 5R01GM062534 to G.J.H.), by the Ellison Medical Foundation (A.A.A.), and by a kind gift from Kathryn W. Davis (G.J.H.).\n\nPublished - Muerdter2012p16789Rna.pdf
Supplemental Material - Muerdter_suppl_figures.pdf
Supplemental Material - Supp_Fig_Legends.docx
", "abstract": "In animals a discrete class of small RNAs, the piwi-interacting RNAs (piRNAs), guard germ cell genomes against the activity of mobile genetic elements. piRNAs are generated, via an unknown mechanism, from apparently single-stranded precursors that arise from discrete genomic loci, termed piRNA clusters. Presently, little is known about the signals that distinguish a locus as a source of piRNAs. It is also unknown how individual piRNAs are selected from long precursor transcripts. To address these questions, we inserted new artificial sequence information into piRNA clusters and introduced these marked clusters as transgenes into heterologous genomic positions in mice and flies. Profiling of piRNA from transgenic animals demonstrated that artificial sequences were incorporated into the piRNA repertoire. Transgenic piRNA clusters are functional in non-native genomic contexts in both mice and flies, indicating that the signals that define piRNA generative loci must lie within the clusters themselves rather than being implicit in their genomic position. Comparison of transgenic animals that carry insertions of the same artificial sequence into different ectopic piRNA-generating loci showed that both local and long-range sequence environments inform the generation of individual piRNAs from precursor transcripts.", "date": "2012-01", "date_type": "published", "publication": "RNA", "volume": "18", "number": "1", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "42-52", "id_number": "CaltechAUTHORS:20120126-110548127", "issn": "1355-8382", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20120126-110548127", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Volkswagen Foundation" }, { "agency": "Boehringer Ingelheim Fonds" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "NIH", "grant_number": "R00 HD057233" }, { "agency": "NIH", "grant_number": "5R01GM062534" }, { "agency": "Ellison Medical Foundation" } ] }, "doi": "10.1261/rna.029769.111", "pmcid": "PMC3261743", "primary_object": { "basename": "Supp_Fig_Legends.docx", "url": "https://authors.library.caltech.edu/records/q2cdk-1k022/files/Supp_Fig_Legends.docx" }, "related_objects": [ { "basename": "Muerdter2012p16789Rna.pdf", "url": "https://authors.library.caltech.edu/records/q2cdk-1k022/files/Muerdter2012p16789Rna.pdf" }, { "basename": "Muerdter_suppl_figures.pdf", "url": "https://authors.library.caltech.edu/records/q2cdk-1k022/files/Muerdter_suppl_figures.pdf" } ], "resource_type": "article", "pub_year": "2012", "author_list": "Muerdter, Felix; Olovnikov, Ivan; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/5e1xr-73z82", "eprint_id": 23340, "eprint_status": "archive", "datestamp": "2023-08-19 06:00:14", "lastmod": "2023-10-23 19:01:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Siomi-Mikiko-C", "name": { "family": "Siomi", "given": "Mikiko C." }, "orcid": "0000-0002-6149-4396" }, { "id": "Sato-Kaoru", "name": { "family": "Sato", "given": "Kaoru" } }, { "id": "Pezic-Dubravka", "name": { "family": "Pezic", "given": "Dubravka" }, "orcid": "0000-0002-9833-8469" }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" } ] }, "title": "PIWI-interacting small RNAs: the vanguard of genome defence", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. \n\nPublished online 23 March 2011.\n\nWe thank H. Siomi, A. Nagao, A. Webster, N. Perkins and\nI. Olovnikov for comments on the manuscript. The work in the\nlaboratory of M.C.S. is supported by Ministry of Education,\nCulture, Sports, Science and Technology (MEXT) grants to K.S. and M.C.S. M.C.S. is supported by the Core Research for\nEvolutional Science and Technology (CREST) programme of the\nJapan Science and Technology Agency (JST). The work in the\nlaboratory of A.A.A. is supported by the US National Institutes of Health (grants DP2 OD007371A and R00 HD057233\u201102 to A.A.A.) and the Ellison Medical Foundation.", "abstract": "PIWI-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs that form the piRNA-induced silencing complex (piRISC) in the germ line of many animal species. The piRISC protects the integrity of the genome from invasion by 'genomic parasites' \u2014 transposable elements \u2014 by silencing them. Owing to their limited expression in gonads and their sequence diversity, piRNAs have been the most mysterious class of small non-coding RNAs regulating RNA silencing. Now, much progress is being made into our understanding of their biogenesis and molecular functions, including the specific subcellular compartmentalization of the piRNA pathway in granular cytoplasmic bodies.", "date": "2011-04", "date_type": "published", "publication": "Nature Reviews. Molecular Cell Biology", "volume": "12", "number": "4", "publisher": "Nature Publishing Group", "pagerange": "246-258", "id_number": "CaltechAUTHORS:20110414-105630858", "issn": "1471-0072", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110414-105630858", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT)" }, { "agency": "Japan Science and Technology Agency (JST)" }, { "agency": "NIH", "grant_number": "DP2 OD007371A" }, { "agency": "NIH", "grant_number": "R00 HD057233\u201102" }, { "agency": "Ellison Medical Foundation" } ] }, "doi": "10.1038/nrm3089", "resource_type": "article", "pub_year": "2011", "author_list": "Siomi, Mikiko C.; Sato, Kaoru; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/fychn-7qe86", "eprint_id": 23363, "eprint_status": "archive", "datestamp": "2023-08-19 05:51:54", "lastmod": "2023-10-23 19:02:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Chan-D-C", "name": { "family": "Chan", "given": "David C." }, "orcid": "0000-0002-0191-2154" } ] }, "title": "piRNAs Meet Mitochondria", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2011 Elsevier Inc. Available online 14 March 2011.", "abstract": "zuc/MitoPLD encodes a conserved enzyme that localizes to mitochondria and hydrolyzes the mitochondria-specific lipid cardiolipin. Surprisingly, zuc/MitoPLD activity is required for Piwi-interacting RNA (piRNA)-mediated silencing of transposable elements in fly and mouse germlines, suggesting that signaling from mitochondria influences the piRNA pathway.", "date": "2011-03-15", "date_type": "published", "publication": "Developmental Cell", "volume": "20", "number": "3", "publisher": "Cell Press", "pagerange": "287-288", "id_number": "CaltechAUTHORS:20110418-113351861", "issn": "1534-5807", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110418-113351861", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1016/j.devcel.2011.03.003", "resource_type": "article", "pub_year": "2011", "author_list": "Aravin, Alexei A. and Chan, David C." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rgje6-f6a39", "eprint_id": 95338, "eprint_status": "archive", "datestamp": "2023-08-22 00:29:54", "lastmod": "2023-10-20 19:09:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rozhkov-N-V", "name": { "family": "Rozhkov", "given": "Nikolay V." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Zelentsova-E-S", "name": { "family": "Zelentsova", "given": "Elena S." } }, { "id": "Schostak-N-G", "name": { "family": "Schostak", "given": "Natalia G." } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "McCombie-W-R", "name": { "family": "McCombie", "given": "W. Richard" } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Evgen'ev-M-B", "name": { "family": "Evgen'ev", "given": "Michael B." } } ] }, "title": "Small RNA-based silencing strategies for transposons in the process of invading Drosophila species", "ispublished": "pub", "full_text_status": "public", "keywords": "Drosophila virilis; piRNA; siRNA; transposon", "note": "\u00a9 2010 RNA Society. Freely available online through the RNA Open Access option. \n\nReceived April 8, 2010; accepted May 21, 2010. \n\nWe thank M. Rooks, Laura Cardone, and Melissa Kramer for help with Illumina sequencing; G. Assaf and O. Tam for help with bioinformatics analysis; and E. Rozhkova for fly husbandry. We also thank members of the Hannon laboratory for helpful discussions. G.J.H. is an investigator of the Howard Hughes Medical institute, and this work was supported by grants from the NIH and by a kind gift from Kathryn W. Davis. Work at the IMB was supported by the Program of Molecular and Cellular Biology RAN. Sequences reported in this study can be accessed using GEO accession number: GSE22067.\n\nPublished - RNA-2010-Rozhkov-1634-45.pdf
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", "abstract": "Colonization of a host by an active transposon can increase mutation rates or cause sterility, a phenotype termed hybrid dysgenesis. As an example, intercrosses of certain Drosophila virilis strains can produce dysgenic progeny. The Penelope element is present only in a subset of laboratory strains and has been implicated as a causative agent of the dysgenic phenotype. We have also introduced Penelope into Drosophila melanogaster, which are otherwise naive to the element. We have taken advantage of these natural and experimentally induced colonization processes to probe the evolution of small RNA pathways in response to transposon challenge. In both species, Penelope was predominantly targeted by endo-small-interfering RNAs (siRNAs) rather than by piwi-interacting RNAs (piRNAs). Although we do observe correlations between Penelope transcription and dysgenesis, we could not correlate differences in maternally deposited Penelope piRNAs with the sterility of progeny. Instead, we found that strains that produced dysgenic progeny differed in their production of piRNAs from clusters in subtelomeric regions, possibly indicating that changes in the overall piRNA repertoire underlie dysgenesis. Considered together, our data reveal unexpected plasticity in small RNA pathways in germ cells, both in the character of their responses to invading transposons and in the piRNA clusters that define their ability to respond to mobile elements.", "date": "2010-08", "date_type": "published", "publication": "RNA", "volume": "16", "number": "8", "publisher": "RNA Society", "pagerange": "1634-1645", "id_number": "CaltechAUTHORS:20190508-084004819", "issn": "1355-8382", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-084004819", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH" } ] }, "doi": "10.1261/rna.2217810", "pmcid": "PMC2905761", "primary_object": { "basename": "Figure_S1_fixed.pdf", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/Figure_S1_fixed.pdf" }, "related_objects": [ { "basename": "Figure_S2_fixed.pdf", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/Figure_S2_fixed.pdf" }, { "basename": "RNA-2010-Rozhkov-1634-45.pdf", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/RNA-2010-Rozhkov-1634-45.pdf" }, { "basename": "Supp_Legends.doc", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/Supp_Legends.doc" }, { "basename": "Table_S1_fixed.pdf", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/Table_S1_fixed.pdf" }, { "basename": "Table_S2_fixed.pdf", "url": "https://authors.library.caltech.edu/records/rgje6-f6a39/files/Table_S2_fixed.pdf" } ], "resource_type": "article", "pub_year": "2010", "author_list": "Rozhkov, Nikolay V.; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2sn1p-w4x89", "eprint_id": 95346, "eprint_status": "archive", "datestamp": "2023-08-21 23:44:37", "lastmod": "2023-10-20 20:09:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rozhkov-N-V", "name": { "family": "Rozhkov", "given": "N. V." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "R." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "G. J." } }, { "id": "Sokolova-O-N", "name": { "family": "Sokolova", "given": "O. N." } }, { "id": "Zelentsova-E-S", "name": { "family": "Zelentsova", "given": "E. S." } }, { "id": "Shostak-N-G", "name": { "family": "Shostak", "given": "N. G." } }, { "id": "Evgen'ev-M-B", "name": { "family": "Evgen'ev", "given": "M. B." } } ] }, "title": "RNA interference system differently responds to the same mobile element in distant Drosophila species", "ispublished": "pub", "full_text_status": "public", "keywords": "Host Genome; DOKLADY Biochemistry; Short RNAs; Active Copy; Howard Hughes Medical Institute", "note": "\u00a9 2010 Pleiades Publishing, Ltd. Original Russian Text \u00a9 N.V. Rozhkov, A.A. Aravin, R. Sachidanandam, G.J. Hannon, O.N. Sokolova, E.S. Zelentsova, N.G. Shostak, M.B. Evgen'ev, 2010, published in Doklady Akademii Nauk, 2010, Vol. 431, No. 3, pp. 411\u2013413. \n\nPresented by Academician Yu.V. Ilyin August 13, 2009. \n\nReceived October 12, 2009.\n\nAccepted Version - nihms255018.pdf
", "abstract": "Mobile genetic elements (MEs) account for a considerable portion of the genome in almost all organisms studied in this respect [1, 2]. During evolution, organisms acquired numerous protective mechanisms that control the activity of various MEs and prevent\ntheir transpositions [3, 4].", "date": "2010-04-10", "date_type": "published", "publication": "Doklady Biochemistry and Biophysics", "volume": "431", "number": "1", "publisher": "Pleiades Publishing Ltd", "pagerange": "79-81", "id_number": "CaltechAUTHORS:20190508-105608053", "issn": "1607-6729", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-105608053", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "doi": "10.1134/s1607672910020079", "pmcid": "PMC2998894", "primary_object": { "basename": "nihms255018.pdf", "url": "https://authors.library.caltech.edu/records/2sn1p-w4x89/files/nihms255018.pdf" }, "resource_type": "article", "pub_year": "2010", "author_list": "Rozhkov, N. V.; Aravin, A. A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/9xg8x-0p422", "eprint_id": 95347, "eprint_status": "archive", "datestamp": "2023-08-19 00:51:55", "lastmod": "2023-10-20 20:09:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasily V." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Arginine methylation as a molecular signature of the Piwi small RNA pathway", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2009 Taylor & Francis. \n\nSubmitted: 07/31/09; Accepted: 09/21/09. Published online: 15 Dec 2009. \n\nThis work was supported by grants from the National Institutes of Health to G.J.H. and an NIH Pathway to Independence Award K99HD057233 to A.A.A.\n\nAccepted Version - nihms249942.pdf
", "abstract": "Almost all eukaryotes have small RNA pathways that regulate expression of protein-coding genes, control the activity of endogenous transposable elements and fight exogenous viral infection. Despite diversity of small RNA pathways functions and mechanisms, their core is conserved throughout evolution: it is an effector complex containing a small RNA that is tightly bound to a member of the Argonaute protein family. The small RNA provides specificity by recognition of complementary RNA targets. The Argonaute protein provides the effector function; it either destroys target RNA directly using its endonuclease activity or inhibits it indirectly, for example by recruiting additional protein factors that cause translational repression (in animals) or inducing changes in chromatin structure (in fission yeast and possibly some plants).", "date": "2009-12-15", "date_type": "published", "publication": "Cell Cycle", "volume": "8", "number": "24", "publisher": "Landes Bioscience", "pagerange": "4003-4004", "id_number": "CaltechAUTHORS:20190508-111053464", "issn": "1538-4101", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-111053464", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99HD057233" } ] }, "doi": "10.4161/cc.8.24.10146", "pmcid": "PMC2993161", "primary_object": { "basename": "nihms249942.pdf", "url": "https://authors.library.caltech.edu/records/9xg8x-0p422/files/nihms249942.pdf" }, "resource_type": "article", "pub_year": "2009", "author_list": "Vagin, Vasily V.; Hannon, Gregory J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/pk1z4-hza25", "eprint_id": 95348, "eprint_status": "archive", "datestamp": "2023-08-19 00:50:34", "lastmod": "2023-10-20 23:26:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "van-der-Heijden-G-W", "name": { "family": "van der Heijden", "given": "Godfried W." } }, { "id": "Casta\u00f1eda-J", "name": { "family": "Casta\u00f1eda", "given": "Julio" } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasily V." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Bortvin-A", "name": { "family": "Bortvin", "given": "Alex" } } ] }, "title": "Cytoplasmic Compartmentalization of the Fetal piRNA Pathway in Mice", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2009 Aravin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived July 28, 2009; Accepted November 11, 2009; Published December 11, 2009. \n\nGJH is an investigator of the Howard Hughes Medical Institute. This work was supported by Carnegie Institution of Washington, grants from the National Institutes of Health to GJH, and by an NIH Pathway to Independence Award K99HD057233 to AAA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. \n\nThe authors have declared that no competing interests exist. \n\nWe thank S.L. Martin, D. Pezic, S. Chuma, E.K. Chan, and S. Tajima for sharing their antibodies. We thank Eugenia Dikovsky and the animal facility staff for their invaluable help and Michael Sepanski for assistance and expertise with EM studies (Carnegie Institution). We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology and Michelle Rooks, Dick Mccombie, Danea Rabbolini, and Laura Cardone for help with Illumina sequencing (CSHL). \n\nAuthor Contributions: Conceived and designed the experiments: AAA GWvdH GJH AB. Performed the experiments: AAA GWvdH AB. Analyzed the data: AAA GWvdH GJH AB. Contributed reagents/materials/analysis tools: JC VVV. Wrote the paper: AAA GWvdH GJH AB.\n\nPublished - journal.pgen.1000764.PDF
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", "abstract": "Derepression of transposable elements (TEs) in the course of epigenetic reprogramming of the mouse embryonic germline necessitates the existence of a robust defense that is comprised of PIWI/piRNA pathway and de novo DNA methylation machinery. To gain further insight into biogenesis and function of piRNAs, we studied the intracellular localization of piRNA pathway components and used the combination of genetic, molecular, and cell biological approaches to examine the performance of the piRNA pathway in germ cells of mice lacking Maelstrom (MAEL), an evolutionarily conserved protein implicated in transposon silencing in fruit flies and mice. Here we show that principal components of the fetal piRNA pathway, MILI and MIWI2 proteins, localize to two distinct types of germinal cytoplasmic granules and exhibit differential association with components of the mRNA degradation/translational repression machinery. The first type of granules, pi-bodies, contains the MILI-TDRD1 module of the piRNA pathway and is likely equivalent to the enigmatic \"cementing material\" first described in electron micrographs of rat gonocytes over 35 years ago. The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins. piP-bodies are found predominantly in the proximity of pi-bodies and the two frequently share mouse VASA homolog (MVH) protein, an RNA helicase. In Mael-mutant gonocytes, MIWI2, TDRD9, and MVH are lost from piP-bodies, whereas no effects on pi-body composition are observed. Further analysis revealed that MAEL appears to specifically facilitate MIWI2-dependent aspects of the piRNA pathway including biogenesis of secondary piRNAs, de novo DNA methylation, and efficient downregulation of TEs. Cumulatively, our data reveal elaborate cytoplasmic compartmentalization of the fetal piRNA pathway that relies on MAEL function.", "date": "2009-12-11", "date_type": "published", "publication": "PLOS Genetics", "volume": "5", "number": "12", "publisher": "Public Library of Science", "pagerange": "Art. No. e1000764", "id_number": "CaltechAUTHORS:20190508-111702371", "issn": "1553-7404", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-111702371", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Carnegie Institution of Washington" }, { "agency": "NIH", "grant_number": "K99HD057233" } ] }, "doi": "10.1371/journal.pgen.1000764", "pmcid": "PMC2785470", "primary_object": { "basename": "journal.pgen.1000764.PDF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.PDF" }, "related_objects": [ { "basename": "journal.pgen.1000764.s001.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s001.TIF" }, { "basename": "journal.pgen.1000764.s002.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s002.TIF" }, { "basename": "journal.pgen.1000764.s004.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s004.TIF" }, { "basename": "journal.pgen.1000764.s009.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s009.TIF" }, { "basename": "journal.pgen.1000764.s003.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s003.TIF" }, { "basename": "journal.pgen.1000764.s005.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s005.TIF" }, { "basename": "journal.pgen.1000764.s006.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s006.TIF" }, { "basename": "journal.pgen.1000764.s007.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s007.TIF" }, { "basename": "journal.pgen.1000764.s008.TIF", "url": "https://authors.library.caltech.edu/records/pk1z4-hza25/files/journal.pgen.1000764.s008.TIF" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Aravin, Alexei A.; van der Heijden, Godfried W.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/24ezg-vxd42", "eprint_id": 95349, "eprint_status": "archive", "datestamp": "2023-08-21 22:01:21", "lastmod": "2023-10-20 20:09:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasily V." } }, { "id": "Wohlschlegel-J", "name": { "family": "Wohlschlegel", "given": "James" } }, { "id": "Qu-Jun", "name": { "family": "Qu", "given": "Jun" } }, { "id": "Jonsson-Z", "name": { "family": "Jonsson", "given": "Zophonias" } }, { "id": "Huang-Xinhua", "name": { "family": "Huang", "given": "Xinhua" } }, { "id": "Chuma-Shinichiro", "name": { "family": "Chuma", "given": "Shinichiro" } }, { "id": "Girard-A", "name": { "family": "Girard", "given": "Angelique" } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } } ] }, "title": "Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members", "ispublished": "pub", "full_text_status": "public", "keywords": "Arginine methyation; piRNAs; transposon silencing; tudor proteins", "note": "\u00a9 2009 by Cold Spring Harbor Laboratory Press. Freely available online through the Genes & Development Open Access option. \n\nReceived April 24, 2009; revised version accepted June 8. 2009. Published in Advance July 7, 2009. \n\nWe thank S.L. Martin, J. Wang, B.R. Cullen, A. Bortvin, and M. Fritzler for sharing antibodies, and N. Nakatsuji, T. Tanaka, and M. Hosokawa for tissues and Tudor mutant animals. We thank Sang Yong Kim (CSHL) for generating transgenic animals. We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology, and Michelle Rooks, Dick Mccombie, Danea Rebbolini, and Laura Cardone for help with Illumina sequencing. We thank Katalin Fejes Toth, Nikolay Rozhkov, and Antoine Molaro for help with experiments and illustrations, and Assaf Gordon for help with data analysis. S.C. is supported by Grants-in-Aid from MEXT, Japan; J.W. was supported by funds from the Jonsson Cancer Center at UCLA; and J.Q. is supported by the University at Buffalo Center of Protein Therapeutics grant. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by a kind gift from Kathryn W. Davis and grants from the National Institutes of Health to G.J.H., and an NIH Pathway to Independence Award K99HD057233 to A.A.A.\n\nPublished - Genes_Dev.-2009-Vagin-1749-62.pdf
Supplemental Material - VaginSuppMat.pdf
", "abstract": "In germ cells, Piwi proteins interact with a specific class of small noncoding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. Basic models describe the overall operation of piRNA pathways. However, the protein compositions of Piwi complexes, the critical protein\u2013protein interactions that drive small RNA production and target recognition, and the precise molecular consequences of conserved localization to germline structures, call nuage, remains poorly understood. We purified the three murine Piwi family proteins, MILI, MIWI, and MIWI2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with PRMT5/WDR77, an enzyme that dimethylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their N termini. These modifications are essential to direct complex formation with specific members of the Tudor protein family. Recognition of methylarginine marks by Tudor proteins can drive the localization of Piwi proteins to cytoplasmic foci in an artificial setting, supporting a role for this interaction in Piwi localization to nuage, a characteristic that correlates with proper operation of the piRNA pathway and transposon silencing in multiple organisms.", "date": "2009-08-01", "date_type": "published", "publication": "Genes and Development", "volume": "23", "number": "15", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "1749-1762", "id_number": "CaltechAUTHORS:20190508-112900956", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-112900956", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT)" }, { "agency": "University of California Los Angeles (UCLA)" }, { "agency": "University at Buffalo" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Kathryn W. Davis" }, { "agency": "NIH", "grant_number": "K99HD057233" } ] }, "doi": "10.1101/gad.1814809", "pmcid": "PMC2720255", "primary_object": { "basename": "Genes_Dev.-2009-Vagin-1749-62.pdf", "url": "https://authors.library.caltech.edu/records/24ezg-vxd42/files/Genes_Dev.-2009-Vagin-1749-62.pdf" }, "related_objects": [ { "basename": "VaginSuppMat.pdf", "url": "https://authors.library.caltech.edu/records/24ezg-vxd42/files/VaginSuppMat.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "Vagin, Vasily V.; Wohlschlegel, James; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/kr03m-btp75", "eprint_id": 95351, "eprint_status": "archive", "datestamp": "2023-08-20 00:00:59", "lastmod": "2023-10-20 20:09:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brennecke-J", "name": { "family": "Brennecke", "given": "Julius" } }, { "id": "Malone-C-D", "name": { "family": "Malone", "given": "Colin D." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Stark-A", "name": { "family": "Stark", "given": "Alexander" } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "An Epigenetic Role for Maternally Inherited piRNAs in Transposon Silencing", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2008 American Association for the Advancement of Science. \n\nReceived 26 August 2008; accepted 27 October 2008. \n\nWe thank M. Rooks and D. McCombie (CSHL) for help with deep sequencing, S. Jensen and S. Ronsseray for fly stocks and helpful discussions, and D. Finnegan for the I-element ORF-1 antibody. J.B. is supported by a fellowship from The Ernst Schering Foundation, C.D.M. is a Beckman fellow of the Watson School of Biological Sciences and is supported by an NSF Graduate Research Fellowship, and A.S. is supported by a Human Frontier Science Program fellowship. This work was supported by grants from NIH to G.J.H. and A.A.A. and a kind gift from K. W. Davis (to G.J.H.). Small RNA libraries are deposited at Gene Expression Omnibus (accession no. GSE13081, data sets GSM327620 to GSM327634).\n\nAccepted Version - nihms162951.pdf
Supplemental Material - Brennecke.SOM.pdf
", "abstract": "In plants and mammals, small RNAs indirectly mediate epigenetic inheritance by specifying cytosine methylation. We found that small RNAs themselves serve as vectors for epigenetic information. Crosses between Drosophila strains that differ in the presence of a particular transposon can produce sterile progeny, a phenomenon called hybrid dysgenesis. This phenotype manifests itself only if the transposon is paternally inherited, suggesting maternal transmission of a factor that maintains fertility. In both P- and I-element\u2013mediated hybrid dysgenesis models, daughters show a markedly different content of Piwi-interacting RNAs (piRNAs) targeting each element, depending on their parents of origin. Such differences persist from fertilization through adulthood. This indicates that maternally deposited piRNAs are important for mounting an effective silencing response and that a lack of maternal piRNA inheritance underlies hybrid dysgenesis.", "date": "2008-11-28", "date_type": "published", "publication": "Science", "volume": "322", "number": "5906", "publisher": "American Association for the Advancement of Science", "pagerange": "1387-1392", "id_number": "CaltechAUTHORS:20190508-133015405", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-133015405", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ernst Schering Foundation" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Human Frontier Science Program" }, { "agency": "Kathryn W. Davis" } ] }, "doi": "10.1126/science.1165171", "pmcid": "PMC2805124", "primary_object": { "basename": "Brennecke.SOM.pdf", "url": "https://authors.library.caltech.edu/records/kr03m-btp75/files/Brennecke.SOM.pdf" }, "related_objects": [ { "basename": "nihms162951.pdf", "url": "https://authors.library.caltech.edu/records/kr03m-btp75/files/nihms162951.pdf" } ], "resource_type": "article", "pub_year": "2008", "author_list": "Brennecke, Julius; Malone, Colin D.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/h4gtm-pvc17", "eprint_id": 95352, "eprint_status": "archive", "datestamp": "2023-08-22 13:09:13", "lastmod": "2023-10-20 20:09:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Sachidanandam-Ravi", "name": { "family": "Sachidanandam", "given": "Ravi" }, "orcid": "0000-0001-9844-4459" }, { "id": "Bourc'his-D\u00e9borah", "name": { "family": "Bourc'his", "given": "Deborah" }, "orcid": "0000-0001-9499-7291" }, { "id": "Schaefer-Christopher", "name": { "family": "Schaefer", "given": "Christopher" } }, { "id": "Pezic-Dubravka", "name": { "family": "Pezic", "given": "Dubravka" }, "orcid": "0000-0002-9833-8469" }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Bestor-Timothy", "name": { "family": "Bestor", "given": "Timothy" } }, { "id": "Hannon-Gregory-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice", "ispublished": "pub", "full_text_status": "public", "keywords": "DNA; RNA; Proteins", "note": "\u00a9 2008 Elsevier Inc. \n\nReceived 2 June 2008, Revised 5 September 2008, Accepted 10 September 2008, Available online 25 September 2008. \n\nWe thank Sang Yong Kim (Cold Spring Harbor Laboratory, CSHL) for generating transgenic animals. We thank Maria Mosquera, Lisa Bianco, Jodi Coblentz, and Gula Nourjanova (CSHL) for animal assistance and histology. We thank Stephen Hearn (CSHL) for microscopy assistance and Emily Hodges, Michelle Rooks, Dick Mccombie, Danea Rebolini, and Laura Cardone for help with Illumina sequencing. We thank Catherine Schlingheyde for help with experiments and members of the Hannon laboratory, especially Antoine Molaro, for comments on the manuscript. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the National Institutes of Health (NIH) to G.J.H. and an NIH Pathway to Independence Award K99HD057233 to A.A.A. \n\nAccession Numbers: Sequences reported in this manuscript are available in the Gene Expression Omnibus under accession number GSE12757.\n\nAccepted Version - nihms72596.pdf
Supplemental Material - 1-s2.0-S1097276508006199-mmc1.pdf
", "abstract": "piRNAs and Piwi proteins have been implicated in transposon control and are linked to transposon methylation in mammals. Here we examined the construction of the piRNA system in the restricted developmental window in which methylation patterns are set during mammalian embryogenesis. We find robust expression of two Piwi family proteins, MIWI2 and MILI. Their associated piRNA profiles reveal differences from Drosophila wherein large piRNA clusters act as master regulators of silencing. Instead, in mammals, dispersed transposon copies initiate the pathway, producing primary piRNAs, which predominantly join MILI in the cytoplasm. MIWI2, whose nuclear localization and association with piRNAs depend upon MILI, is enriched for secondary piRNAs antisense to the elements that it controls. The Piwi pathway lies upstream of known mediators of DNA methylation, since piRNAs are still produced in dnmt3L mutants, which fail to methylate transposons. This implicates piRNAs as specificity determinants of DNA methylation in germ cells.", "date": "2008-09-26", "date_type": "published", "publication": "Molecular Cell", "volume": "31", "number": "6", "publisher": "Cell Press", "pagerange": "785-799", "id_number": "CaltechAUTHORS:20190508-133919077", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-133919077", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "K99HD057233" } ] }, "doi": "10.1016/j.molcel.2008.09.003", "pmcid": "PMC2730041", "primary_object": { "basename": "1-s2.0-S1097276508006199-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/h4gtm-pvc17/files/1-s2.0-S1097276508006199-mmc1.pdf" }, "related_objects": [ { "basename": "nihms72596.pdf", "url": "https://authors.library.caltech.edu/records/h4gtm-pvc17/files/nihms72596.pdf" } ], "resource_type": "article", "pub_year": "2008", "author_list": "Aravin, Alexei A.; Sachidanandam, Ravi; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/c2ps4-2nj31", "eprint_id": 95353, "eprint_status": "archive", "datestamp": "2023-08-19 22:45:31", "lastmod": "2023-10-20 20:09:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tam-O-H", "name": { "family": "Tam", "given": "Oliver H." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Stein-P", "name": { "family": "Stein", "given": "Paula" } }, { "id": "Girard-A", "name": { "family": "Girard", "given": "Angelique" } }, { "id": "Murchison-E-P", "name": { "family": "Murchison", "given": "Elizabeth P." } }, { "id": "Cheloufi-S", "name": { "family": "Cheloufi", "given": "Sihem" } }, { "id": "Hodges-E", "name": { "family": "Hodges", "given": "Emily" } }, { "id": "Anger-M", "name": { "family": "Anger", "given": "Martin" } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Schultz-R-M", "name": { "family": "Schultz", "given": "Richard M." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2008 Nature Publishing Group. \n\nReceived 01 November 2007; Accepted 07 March 2008; Published\n10 April 2008. \n\nWe thank members of the Hannon laboratory for discussions. O.H.T. is a Bristol-Meyers Squibb fellow and A.G. is a Florence Gould Foundation Scholar of the Watson School of Biological Sciences. E.P.M. is supported by a fellowship from the Australian-American Association. This work was supported in part by grants from the NIH (R.M.S. and G.J.H.) and gifts from Kathryn W. Davis and the Stanley family (G.J.H. and E.H.). G.J.H. is an Investigator of the Howard Hughes Medical Institute. \n\nOliver H. Tam & Alexei A. Aravin: These authors contributed equally to this work.\n\nAccepted Version - nihms249583.pdf
Supplemental Material - nature06904-s1.pdf
", "abstract": "Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways. Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute-mediated catalysis in mammals.", "date": "2008-05-22", "date_type": "published", "publication": "Nature", "volume": "453", "number": "7194", "publisher": "Nature Publishing Group", "pagerange": "534-538", "id_number": "CaltechAUTHORS:20190508-134616985", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-134616985", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Bristol-Myers Squibb" }, { "agency": "Florence Gould Foundation" }, { "agency": "Australian-American Association" }, { "agency": "Kathryn W. Davis" }, { "agency": "Stanley Family" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1038/nature06904", "pmcid": "PMC2981145", "primary_object": { "basename": "nature06904-s1.pdf", "url": "https://authors.library.caltech.edu/records/c2ps4-2nj31/files/nature06904-s1.pdf" }, "related_objects": [ { "basename": "nihms249583.pdf", "url": "https://authors.library.caltech.edu/records/c2ps4-2nj31/files/nihms249583.pdf" } ], "resource_type": "article", "pub_year": "2008", "author_list": "Tam, Oliver H.; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n470c-mkq26", "eprint_id": 95354, "eprint_status": "archive", "datestamp": "2023-08-22 11:34:42", "lastmod": "2023-10-20 20:09:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." }, "orcid": "0000-0002-6956-8257" }, { "id": "Bourc'his-D\u00e9borah", "name": { "family": "Bourc'his", "given": "D\u00e9borah" }, "orcid": "0000-0001-9499-7291" } ] }, "title": "Small RNA guides for de novo DNA methylation in mammalian germ cells", "ispublished": "pub", "full_text_status": "public", "keywords": "Piwi; piRNA; retrotransposon; DNA methylation; spermatogenesis", "note": "\u00a9 2008 by Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, http://creativecommons.org/licenses/by-nc/4.0/). \n\nWe thank Christopher Schaefer for critical reading of the manuscript and discussions. Research in D.B.'s laboratory is supported by EURYI grants. We apologize to colleagues who were not directly cited due to the size limitation of the perspective format.\n\nPublished - Genes_Dev.-2008-Aravin-970-5.pdf
", "abstract": "Cytosine methylation provides a stable, heritable, and reversible mark for transcriptional repression. Reprogramming of the methylation repertoire at each passage through the germline is a mammalian characteristic. An erasure step allows the acquisition of an epigenetic state unique to the germ cell lineage and central to the transmission of totipotency over generations. Subsequent initiation of gametic methylation has a major impact on fertility, by silencing parasitic transposable elements (TEs) and providing a parental mark for the monoallelic expression of imprinted genes. To control the overwhelming genomic contribution of TEs and their deleterious effects on gamete integrity, a variety of repressive mechanisms, including DNA methylation in mammals, have been developed over the course of evolution to lead to their suppression.\n\nGametic de novo methylation involves the activity of the DNA methyltransferases Dnmt3A and Dnmt3B, assisted by their regulatory factor Dnmt3L. Studies based on structural, biochemical, and DNA analyses provided information as to how these proteins functionally interact to add methyl groups on cytosines within CG dinucleotides. Besides this general recognition of CG sites, additional signals targeting DNA methylation to specific genomic sequences are progressively elucidated. Specific histone modifications and energy-dependent chromatin remodeling enzymes have been shown to regulate the accessibility of DNA methyltransferases to their substrates. A specific class of small RNAs, the piwi-interacting RNAs (piRNAs), was most recently proposed to guide DNA methylation in male germ cells in the mouse. The developmental analysis performed by Kuramochi-Miyagawa et al. (2008) in the context of normal and Piwi-mutant spermatogenesis, published in the previous issue of Genes & Development, definitely supports the existence of an RNA-directed pathway triggering the initiation of DNA methylation in the mammalian germline. The different pieces of the puzzle now lay on the table. Deciphering how these different pieces connect together to control the establishment of gametic methylation patterns at the right time and at the right place will be the next exciting challenge in the field.", "date": "2008-04-15", "date_type": "published", "publication": "Genes and Development", "volume": "22", "number": "8", "publisher": "Cold Spring Harbor Laboratory Press", "pagerange": "970-975", "id_number": "CaltechAUTHORS:20190508-140200614", "issn": "0890-9369", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190508-140200614", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "European Young Investigator Awards (EURYI)" } ] }, "doi": "10.1101/gad.1669408", "pmcid": "PMC2732394", "primary_object": { "basename": "Genes_Dev.-2008-Aravin-970-5.pdf", "url": "https://authors.library.caltech.edu/records/n470c-mkq26/files/Genes_Dev.-2008-Aravin-970-5.pdf" }, "resource_type": "article", "pub_year": "2008", "author_list": "Aravin, Alexei A. and Bourc'his, D\u00e9borah" }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/ajkhb-wnk05", "eprint_id": 95361, "eprint_status": "archive", "datestamp": "2023-08-19 21:58:03", "lastmod": "2023-10-20 20:10:06", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Olson-A-J", "name": { "family": "Olson", "given": "A. J." } }, { "id": "Brennecke-J", "name": { "family": "Brennecke", "given": "J." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "G. J." } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "R." } } ] }, "title": "Analysis of Large-Scale Sequencing of Small RNAs", "ispublished": "unpub", "full_text_status": "restricted", "note": "\u00a9 2008 World Scientific Publishing Company. \n\nThe authors acknowledge the help of Ted Roeder and Ankit Patel with various aspects of the front end for the web-based software and the anonymous reviewers for suggesting numerous improvements to the manuscript.", "abstract": "The advent of large-scale sequencing has opened up new areas of research, such as the study of Piwi-interacting small RNAs (piRNAs). piRNAs are longer than miRNAs, close to 30 nucleotides in length, involved in various functions, such as the suppression of transposons in germline 3,4,5. Since a large number of them (many tens of thousands) are generated from a wide range of positions in the genome, large-scale sequencing is the only way to study them. The key to understanding their genesis and biological roles is efficient analysis, which is complicated by the large volumes of sequence data. Taking account of the underlying biology is also important. We describe here novel analyses techniques and tools applied to small RNAs from germ cells in D. melanogaster, that allowed us to infer mechanism and biological function.", "date": "2008-01", "date_type": "published", "publisher": "World Scientific", "place_of_pub": "Hackensack, NJ", "pagerange": "126-136", "id_number": "CaltechAUTHORS:20190509-081714112", "isbn": "9789812776082", "book_title": "Pacific Symposium on Biocomputing 2008", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-081714112", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "contributors": { "items": [ { "id": "Altman-R", "name": { "family": "Altman", "given": "Russ" } } ] }, "doi": "10.1142/9789812776136_0014", "resource_type": "book_section", "pub_year": "2008", "author_list": "Olson, A. J.; Brennecke, J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/b4k9e-zvw59", "eprint_id": 95359, "eprint_status": "archive", "datestamp": "2023-08-19 21:54:03", "lastmod": "2024-01-14 21:43:08", "type": "book_section", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "G. J." } } ] }, "title": "Small RNA Silencing Pathways in Germ and Stem Cells", "ispublished": "unpub", "full_text_status": "public", "note": "\u00a9 2008 Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, http://creativecommons.org/licenses/by-nc/4.0/). \n\nWe thank members of the Hannon lab for helpful discussions. This work was supported by grants from the National Institutes of Health (NIH) to G.J.H. and an NIH Pathway to Independence Award K99HD057233 to A.A.A.\n\nPublished - 283.full.pdf
", "abstract": "During the past several years, it has become clear that small RNAs guard germ cell genomes from the activity of mobile genetic elements. Indeed, in mammals, a class of small RNAs, known as Piwi-interacting RNAs (piRNAs), forms an innate immune system that discriminates transposons from endogenous genes and selectively silences the former. piRNAs enforce silencing by directing transposon DNA methylation during male germ cell development. As such, piRNAs represent perhaps the only currently known sequence-specific factor for deposition of methylcytosine in mammals. The three mammalian Piwi proteins Miwi2, Mili, and Miwi are required at different stages of germ cell development. Moreover, distinct classes of piRNAs are expressed in developmental waves, with particular generative loci and different sequence content distinguishing piRNAs populations in embryonic germ cells from those that appear during meiosis. Although our understanding of Piwi proteins and piRNA biology have deepened substantially during the last several years, major gaps still exist in our understanding of these enigmatic RNA species.", "date": "2008", "date_type": "published", "publisher": "Cold Spring Harbor Laboratory", "place_of_pub": "New York, NY", "pagerange": "283-290", "id_number": "CaltechAUTHORS:20190509-074849509", "isbn": "978-087969862-1", "book_title": "Control and regulation of stem cells", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-074849509", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K99HD057233" } ] }, "contributors": { "items": [ { "id": "Grodzicker-T", "name": { "family": "Grodzicker", "given": "Terri" } }, { "id": "Stewart-D", "name": { "family": "Stewart", "given": "David" } }, { "id": "Stillman-B", "name": { "family": "Stillman", "given": "Bruce" } } ] }, "doi": "10.1101/sqb.2008.73.058", "primary_object": { "basename": "283.full.pdf", "url": "https://authors.library.caltech.edu/records/b4k9e-zvw59/files/283.full.pdf" }, "resource_type": "book_section", "pub_year": "2008", "author_list": "Aravin, A. A. and Hannon, G. J." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/aa95d-pyv78", "eprint_id": 95363, "eprint_status": "archive", "datestamp": "2023-08-19 21:24:55", "lastmod": "2023-10-20 20:10:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } }, { "id": "Brennecke-J", "name": { "family": "Brennecke", "given": "Julius" } } ] }, "title": "The Piwi-piRNA Pathway Provides an Adaptive Defense in the Transposon Arms Race", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Association for the Advancement of Science. \n\nReceived 14 June 2007; accepted 17 August 2007. \n\nWe thank members of the Hannon lab for stimulating discussions. A.A.A. was supported by a Cold Spring Harbor Laboratory Association Fellowship and J.B. was supported by the Schering Foundation. This work was supported by grants from the NIH (G.J.H.) and by a generous gift from Kathyrn W. Davis.\n\nSupplemental Material - Aravin.SOM.pdf
", "abstract": "Increasingly complex networks of small RNAs act through RNA-interference (RNAi) pathways to regulate gene expression, to mediate antiviral responses, to organize chromosomal domains, and to restrain the spread of selfish genetic elements. Historically, RNAi has been defined as a response to double-stranded RNA. However, some small RNA species may not arise from double-stranded RNA precursors. Yet, like microRNAs and small interfering RNAs, such species guide Argonaute proteins to silencing targets through complementary base-pairing. Silencing can be achieved by corecruitment of accessory factors or through the activity of Argonaute itself, which often has endonucleolytic activity. As a specific and adaptive regulatory system, RNAi is used throughout eukarya, which indicates a long evolutionary history. A likely function of RNAi throughout that history is to protect the genome from both pathogenic and parasitic invaders.", "date": "2007-11-02", "date_type": "published", "publication": "Science", "volume": "318", "number": "5851", "publisher": "American Association for the Advancement of Science", "pagerange": "761-764", "id_number": "CaltechAUTHORS:20190509-083948927", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-083948927", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Cold Spring Harbor Laboratory" }, { "agency": "Schering Foundation" }, { "agency": "NIH" }, { "agency": "Kathyrn W. Davis" } ] }, "doi": "10.1126/science.1146484", "primary_object": { "basename": "Aravin.SOM.pdf", "url": "https://authors.library.caltech.edu/records/aa95d-pyv78/files/Aravin.SOM.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Aravin, Alexei A.; Hannon, Gregory J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/re8jc-7r415", "eprint_id": 95378, "eprint_status": "archive", "datestamp": "2023-08-19 20:43:43", "lastmod": "2023-10-20 20:11:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "Mikhail S." } }, { "id": "Lavrov-S-A", "name": { "family": "Lavrov", "given": "Sergey A." } }, { "id": "Stolyarenko-A-D", "name": { "family": "Stolyarenko", "given": "Anastasia D." } }, { "id": "Ryazansky-S-S", "name": { "family": "Ryazansky", "given": "Sergey S." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Tuschl-T", "name": { "family": "Tuschl", "given": "Thomas" } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } } ] }, "title": "Repeat-associated siRNAs cause chromatin silencing of retrotransposons in the Drosophila melanogaster germline", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nReceived: 19 May 2007; Revision Received: 15 July 2007; Accepted: 15 July 2007; Published: 15 August 2007. \n\nWe thank Alla Kalmykova for technical support in isolation of ovarian RNA used for short RNA cloning, Olesya Sokolova and Alina Korbut for help in RT-PCR and ChIP experiments, E.G. Pasyukova for kindly providing flies carrying the copiaLTR-lacZ construct and James M. Mason for help in the manuscript preparation. This work was supported by RAS program for Molecular and Cell Biology, Russian Foundation for Basic Research (05-04-48034), the program of Scientific School support (6113.2006.4) and grant of President of Russian Federation for young scientists (02.120.11.9326). Funding to pay the Open Access publication charges for this article was provided by Russian Foundation for Basic Research (05-04-48034). \n\nConflict of interest statement. None declared.\n\nPublished - gkm576.pdf
Supplemental Material - gkm576_Supplementary_Data.zip
", "abstract": "Silencing of genomic repeats, including transposable elements, in Drosophila melanogaster is mediated by repeat-associated short interfering RNAs (rasiRNAs) interacting with proteins of the Piwi subfamily. rasiRNA-based silencing is thought to be mechanistically distinct from both the RNA interference and microRNA pathways. We show that the amount of rasiRNAs of a wide range of retroelements is drastically reduced in ovaries and testes of flies carrying a mutation in the spn-E gene. To address the mechanism of rasiRNA-dependent silencing of retrotransposons, we monitored their chromatin state in ovaries and somatic tissues. This revealed that the spn-E mutation causes chromatin opening of retroelements in ovaries, resulting in an increase in histone H3 K4 dimethylation and a decrease in histone H3 K9 di/trimethylation. The strongest chromatin changes have been detected for telomeric HeT-A elements that correlates with the most dramatic increase of their transcript level, compared to other mobile elements. The spn-E mutation also causes depletion of HP1 content in the chromatin of transposable elements, especially along HeT-A arrays. We also show that mutations in the genes controlling the rasiRNA pathway cause no derepression of the same retrotransposons in somatic tissues. Our results provide evidence that germinal Piwi-associated short RNAs induce chromatin modifications of their targets.", "date": "2007-08", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "35", "number": "16", "publisher": "Oxford University Press", "pagerange": "5430-5438", "id_number": "CaltechAUTHORS:20190509-130212772", "issn": "1362-4962", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-130212772", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "05-04-48034" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "6113.2006.4" }, { "agency": "President of Russian Federation for Young Scientists", "grant_number": "02.120.11.9326" } ] }, "doi": "10.1093/nar/gkm576", "pmcid": "PMC2018648", "primary_object": { "basename": "gkm576.pdf", "url": "https://authors.library.caltech.edu/records/re8jc-7r415/files/gkm576.pdf" }, "related_objects": [ { "basename": "gkm576_Supplementary_Data.zip", "url": "https://authors.library.caltech.edu/records/re8jc-7r415/files/gkm576_Supplementary_Data.zip" } ], "resource_type": "article", "pub_year": "2007", "author_list": "Klenov, Mikhail S.; Lavrov, Sergey A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rfyrh-83v55", "eprint_id": 95364, "eprint_status": "archive", "datestamp": "2023-08-19 20:11:15", "lastmod": "2023-10-20 20:10:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Girard-A", "name": { "family": "Girard", "given": "Angelique" } }, { "id": "Fejes-T\u00f3th-K", "name": { "family": "Fejes Toth", "given": "Katalin" }, "orcid": "0000-0001-6558-2636" }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "Developmentally Regulated piRNA Clusters Implicate MILI in Transposon Control", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 American Association for the Advancement of Science. \n\nReceived 16 March 2007; accepted 30 March 2007. Published online 19 April 2007. \n\npiRNA sequences are available in the Gene Expression Omnibus (GEO) database (accession # GSE7414). We thank H. Lin (Yale University) for the Mili knockout mouse. A.A.A. is supported by a Cold Spring Harbor Laboratory Association fellowship. A.G. is a Florence Gould Fellow of the Watson School of Biological Sciences. G.J.H. is an HHMI investigator. This work was supported by grants from NIH and from Katherine W. Davis (G.J.H.).\n\nSupplemental Material - Aravin.SOM.pdf
", "abstract": "Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are depleted of repeat sequences, which raises questions about a role for mammalian Piwi's in transposon control. A search for murine small RNAs that might program Piwi proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which MILI catalyzes the formation of piRNA 5\u2032 ends. Mili mutants derepress LINE-1 (L1) and intracisternal A particle and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression.", "date": "2007-05-04", "date_type": "published", "publication": "Science", "volume": "316", "number": "5825", "publisher": "American Association for the Advancement of Science", "pagerange": "744-747", "id_number": "CaltechAUTHORS:20190509-090419753", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-090419753", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Cold Spring Harbor Laboratory" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH" }, { "agency": "Katherine W. Davis" } ] }, "doi": "10.1126/science.1142612", "primary_object": { "basename": "Aravin.SOM.pdf", "url": "https://authors.library.caltech.edu/records/rfyrh-83v55/files/Aravin.SOM.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Aravin, Alexei A.; Sachidanandam, Ravi; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/wjqcw-y8f45", "eprint_id": 95370, "eprint_status": "archive", "datestamp": "2023-08-19 19:52:53", "lastmod": "2023-10-20 20:10:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brennecke-J", "name": { "family": "Brennecke", "given": "Julius" } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Stark-A", "name": { "family": "Stark", "given": "Alexander" } }, { "id": "Dus-M", "name": { "family": "Dus", "given": "Monica" } }, { "id": "Kellis-M", "name": { "family": "Kellis", "given": "Manolis" } }, { "id": "Sachidanandam-R", "name": { "family": "Sachidanandam", "given": "Ravi" } }, { "id": "Hannon-G-J", "name": { "family": "Hannon", "given": "Gregory J." } } ] }, "title": "Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2007 Elsevier Inc. Under an Elsevier user license. \n\nReceived 23 October 2006, Revised 8 December 2006, Accepted 19 January 2007, Available online 8 March 2007. \n\nWe thank members of the Hannon laboratory for helpful discussions and support. Ahmet Denli (CSHL) provided antibodies, and Stuart Shuman (MSKCC) provided the expression vector for Rnl2. We thank Andrew Olson and Ted Roeder for bioinformatic support and Stephen Hearn (CSHL) for assistance with confocal microscopy. J.B. and A.S. are supported by fellowships from the Ernst Schering Foundation. A.A. is supported by a fellowship from the CSHL Association. M.D. is an Engelhorn Scholar of the Watson School of Biological Sciences. G.J.H. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the N.I.H. (G.J.H.). \n\nAccession Numbers: The GenBank accession number for Ago3 in this paper is EF211827. The GEO accession numbers for all piRNAs from this study are GSE6734, GSM154618, GSM154620, GSM154621, and GSM154622.\n\nSupplemental Material - 1-s2.0-S0092867407002577-mmc1.pdf
", "abstract": "Drosophila Piwi-family proteins have been implicated in transposon control. Here, we examine piwi-interacting RNAs (piRNAs) associated with each Drosophila Piwi protein and find that Piwi and Aubergine bind RNAs that are predominantly antisense to transposons, whereas Ago3 complexes contain predominantly sense piRNAs. As in mammals, the majority of Drosophila piRNAs are derived from discrete genomic loci. These loci comprise mainly defective transposon sequences, and some have previously been identified as master regulators of transposon activity. Our data suggest that heterochromatic piRNA loci interact with potentially active, euchromatic transposons to form an adaptive system for transposon control. Complementary relationships between sense and antisense piRNA populations suggest an amplification loop wherein each piRNA-directed cleavage event generates the 5\u2032 end of a new piRNA. Thus, sense piRNAs, formed following cleavage of transposon mRNAs may enhance production of antisense piRNAs, complementary to active elements, by directing cleavage of transcripts from master control loci.", "date": "2007-03-23", "date_type": "published", "publication": "Cell", "volume": "128", "number": "6", "publisher": "Elsevier", "pagerange": "1089-1103", "id_number": "CaltechAUTHORS:20190509-101139052", "issn": "0092-8674", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-101139052", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ernst Schering Foundation" }, { "agency": "Cold Spring Harbor Laboratory" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH" } ] }, "doi": "10.1016/j.cell.2007.01.043", "primary_object": { "basename": "1-s2.0-S0092867407002577-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/wjqcw-y8f45/files/1-s2.0-S0092867407002577-mmc1.pdf" }, "resource_type": "article", "pub_year": "2007", "author_list": "Brennecke, Julius; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/3698m-cds42", "eprint_id": 95379, "eprint_status": "archive", "datestamp": "2023-08-19 14:03:28", "lastmod": "2023-10-20 20:11:26", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "Mikhail S." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasilii V." } }, { "id": "Bantignies-F", "name": { "family": "Bantignies", "given": "Fr\u00e9d\u00e9ric" } }, { "id": "Cavalli-G", "name": { "family": "Cavalli", "given": "Giacomo" }, "orcid": "0000-0003-3709-3469" }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } } ] }, "title": "Dissection of a Natural RNA Silencing Process in the Drosophila melanogaster Germ Line", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2004 American Society for Microbiology. \n\nReceived 12 November 2003; Returned for modification 31 December 2003; Accepted 6 April 2004. \n\nWe thank Leonard Robbins, Yair Dorsett, and Phillip Zamore for text improvements and critical comments. \n\nThis work was supported by grants from the Russian Foundation for Basic Researches (N 02-04-48498), INTAS (N 01-0279), the Russian Foundation for Science School Support (N 2074, 2003.4), the Physics-Chemical Biology Program of RAS, and INTAS young scientist fellowship YSF 00-243 to A.A.A. The work of F.B. and G.C. was supported by grants from the CNRS (ATIPE), the Association pour la Recherche sur le Cancer, and the Human Frontier Science Program Organization.\n\nPublished - Molecular_and_Cellular_Biology-2004-Aravin-6742.full.pdf
", "abstract": "To date, few natural cases of RNA-silencing-mediated regulation have been described. Here, we analyzed repression of testis-expressed Stellate genes by the homologous Suppressors of Stellate [Su(Ste)] repeats that produce sense and antisense short RNAs. The Stellate promoter is dispensable for suppression, but local disturbance of complementarity between the Stellate transcript and the Su(Ste) repeats impairs silencing. Using in situ RNA hybridization, we found temporal control of the expression and spatial distribution of sense and antisense Stellate and Su(Ste) transcripts in germinal cells. Antisense Su(Ste) transcripts accumulate in the nuclei of early spermatocytes before the appearance of sense transcripts. The sense and antisense transcripts are colocalized in the nuclei of mature spermatocytes, placing the initial step of silencing in the nucleus and suggesting formation of double-stranded RNA. Mutations in the aubergine and spindle-E genes, members of the Argonaute and RNA helicase gene families, respectively, impair silencing by eliminating the short Su(Ste) RNA, but have no effect on microRNA production. Thus, different small RNA-containing complexes operate in the male germ line.", "date": "2004-08", "date_type": "published", "publication": "Molecular and Cellular Biology", "volume": "24", "number": "15", "publisher": "American Society for Microbiology", "pagerange": "6742-6750", "id_number": "CaltechAUTHORS:20190509-134457510", "issn": "0270-7306", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-134457510", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "02-04-48498" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-0279" }, { "agency": "Russian Foundation for Science School Support", "grant_number": "2074, 2003.4" }, { "agency": "Russian Academy of Sciences" }, { "agency": "International Association for the Promotion of Cooperation with Scientists from the New Independent States", "grant_number": "YSF 00-243" }, { "agency": "Centre National de la Recherche Scientifique (CNRS)" }, { "agency": "Association pour la Recherche sur le Cancer" }, { "agency": "Human Frontier Science Program" } ] }, "doi": "10.1128/mcb.24.15.6742-6750.2004", "pmcid": "PMC444866", "primary_object": { "basename": "Molecular_and_Cellular_Biology-2004-Aravin-6742.full.pdf", "url": "https://authors.library.caltech.edu/records/3698m-cds42/files/Molecular_and_Cellular_Biology-2004-Aravin-6742.full.pdf" }, "resource_type": "article", "pub_year": "2004", "author_list": "Aravin, Alexei A.; Klenov, Mikhail S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/55rk2-82m70", "eprint_id": 95380, "eprint_status": "archive", "datestamp": "2023-08-19 11:50:10", "lastmod": "2023-10-20 20:11:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Lagos-Quintana-M", "name": { "family": "Lagos-Quintana", "given": "Mariana" } }, { "id": "Yalcin-A", "name": { "family": "Yalcin", "given": "Abdullah" } }, { "id": "Zavolan-M", "name": { "family": "Zavolan", "given": "Mihaela" } }, { "id": "Marks-D", "name": { "family": "Marks", "given": "Debora" } }, { "id": "Snyder-B", "name": { "family": "Snyder", "given": "Ben" } }, { "id": "Gaasterland-T", "name": { "family": "Gaasterland", "given": "Terry" } }, { "id": "Meyer-J", "name": { "family": "Meyer", "given": "Jutta" } }, { "id": "Tuschl-T", "name": { "family": "Tuschl", "given": "Thomas" } } ] }, "title": "Small RNA Profile during Drosophila melanogaster Development", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2003 Cell Press. Published by Elsevier Inc. \n\nReceived 16 June 2003, Revised 23 June 2003, Accepted 27 June 2003, Available online 16 April 2004. \n\nWe thank G. Dowe and M. Killian for sequencing, W. Lendeckel for help on cloning, A. H\u00fcttenhofer for providing D. melanogaster noncoding RNA sequences to facilitate sequence annotation, Y. Dorsett, M. Landthaler, S. Pfeffer, J. Silverman, and J. Martinez for comments on the manuscript, H. J\u00e4ckle, R. Rivera-Pomar, and R. L\u00fchrmann for support. This work was funded by a Bundesministerium und Forschung (BMBF) Biofuture grant number 0311856, Program Physico-Chemical Biology RAS, and an EMBO short term fellowship ASTF 9963 to A.A.\n\nSupplemental Material - 1-s2.0-S1534580703002284-mmc1.pdf
Supplemental Material - 1-s2.0-S1534580703002284-mmc2.pdf
Supplemental Material - 1-s2.0-S1534580703002284-mmc3.pdf
Supplemental Material - 1-s2.0-S1534580703002284-mmc4.pdf
Supplemental Material - 1-s2.0-S1534580703002284-mmc5.pdf
", "abstract": "Small RNAs ranging in size between 20 and 30 nucleotides are involved in different types of regulation of gene expression including mRNA degradation, translational repression, and chromatin modification. Here we describe the small RNA profile of Drosophila melanogaster as a function of development. We have cloned and sequenced over 4000 small RNAs, 560 of which have the characteristics of RNase III cleavage products. A nonredundant set of 62 miRNAs was identified. We also isolated 178 repeat-associated small interfering RNAs (rasiRNAs), which are cognate to transposable elements, satellite and microsatellite DNA, and Suppressor of Stellate repeats, suggesting that small RNAs participate in defining chromatin structure. rasiRNAs are most abundant in testes and early embryos, where regulation of transposon activity is critical and dramatic changes in heterochromatin structure occur.", "date": "2003-08", "date_type": "published", "publication": "Developmental Cell", "volume": "5", "number": "2", "publisher": "Cell Press", "pagerange": "337-350", "id_number": "CaltechAUTHORS:20190509-142555498", "issn": "1534-5807", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-142555498", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Bundesministerium f\u00fcr Bildung und Forschung (BMBF)", "grant_number": "0311856" }, { "agency": "Max Planck Institute" }, { "agency": "European Molecular Biology Organization (EMBO)", "grant_number": "ASTF 9963" } ] }, "doi": "10.1016/s1534-5807(03)00228-4", "primary_object": { "basename": "1-s2.0-S1534580703002284-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/55rk2-82m70/files/1-s2.0-S1534580703002284-mmc1.pdf" }, "related_objects": [ { "basename": "1-s2.0-S1534580703002284-mmc2.pdf", "url": "https://authors.library.caltech.edu/records/55rk2-82m70/files/1-s2.0-S1534580703002284-mmc2.pdf" }, { "basename": "1-s2.0-S1534580703002284-mmc3.pdf", "url": "https://authors.library.caltech.edu/records/55rk2-82m70/files/1-s2.0-S1534580703002284-mmc3.pdf" }, { "basename": "1-s2.0-S1534580703002284-mmc4.pdf", "url": "https://authors.library.caltech.edu/records/55rk2-82m70/files/1-s2.0-S1534580703002284-mmc4.pdf" }, { "basename": "1-s2.0-S1534580703002284-mmc5.pdf", "url": "https://authors.library.caltech.edu/records/55rk2-82m70/files/1-s2.0-S1534580703002284-mmc5.pdf" } ], "resource_type": "article", "pub_year": "2003", "author_list": "Aravin, Alexei A.; Lagos-Quintana, Mariana; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/km785-wzr59", "eprint_id": 95416, "eprint_status": "archive", "datestamp": "2023-08-22 00:27:50", "lastmod": "2023-10-20 20:12:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kogan-G-L", "name": { "family": "Kogan", "given": "G. L." } }, { "id": "Tulin-A-V", "name": { "family": "Tulin", "given": "A. V." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Abramov-Yu-A", "name": { "family": "Abramov", "given": "Yu. A." } }, { "id": "Kalmykova-A-I", "name": { "family": "Kalmykova", "given": "A. I." } }, { "id": "Maisonhaute-C", "name": { "family": "Maisonhaute", "given": "C." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "GATE retrotransposon in Drosophila melanogaster: mobility in heterochromatin and aspects of its expression in germline tissues", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Drosophila melanogaster; Retrotransposon; Heterochromatin; RNA interference", "note": "\u00a9 2003 Springer-Verlag. \n\nReceived: 15 October 2002; Accepted: 27 January 2003; Published online: 14 March 2003. \n\nWe are grateful to M. B. Evgen'ev and B. D. McKee for the gifts of various species of flies. This work was supported by grants from the Russian Foundation for Basic Research (N 00-15-97896, 01-04-22001, 01-04-48514, 02-04-48498, and PICS N1191).", "abstract": "A full-length copy of the retrotransposon GATE was identified as an insertion in the tandemly repeated, heterochromatic, Stellate genes, which are expressed in the testis of Drosophila melanogaster. Sequencing of this heterochromatic GATE copy revealed that it is closely related to the BEL retrotransposon, a representative of the recently defined BEL -like group of LTR retrotransposons. This copy contains identical LTRs, indicating that the insertion is a recent event. By contrast, the euchromatic part of the D. melanogaster genome contains only profoundly damaged GATE copies or fragments of the transposon. The preferential localization of GATE sequences in heterochromatin was confirmed for the other species in themelanogaster subgroup. The level of GATE expression is dramatically increased in ovaries, but not in testes, of spn-E^1 homozygous flies. We speculate that spn-E is involved in the silencing of GATE via an RNA interference mechanism.", "date": "2003-05", "date_type": "published", "publication": "Molecular Genetics and Genomics", "volume": "269", "number": "2", "publisher": "Springer Nature", "pagerange": "234-242", "id_number": "CaltechAUTHORS:20190513-074617352", "issn": "1617-4615", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-074617352", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "00-15-97896" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-22001" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-48514" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "02-04-48498" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "PICS N1191" } ] }, "doi": "10.1007/s00438-003-0827-1", "resource_type": "article", "pub_year": "2003", "author_list": "Kogan, G. L.; Tulin, A. V.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/dcbrw-60386", "eprint_id": 95440, "eprint_status": "archive", "datestamp": "2023-08-19 11:07:50", "lastmod": "2023-10-20 20:14:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Abramov-Y-A", "name": { "family": "Abramov", "given": "Yury A." } }, { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "Mikhail S." } }, { "id": "Kogan-G-L", "name": { "family": "Kogan", "given": "Galina L." } }, { "id": "Lavrov-S-A", "name": { "family": "Lavrov", "given": "Sergei A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "Natalia M." } }, { "id": "Olenkina-O-M", "name": { "family": "Olenkina", "given": "Oxana M." } }, { "id": "Tulin-A-V", "name": { "family": "Tulin", "given": "Alexei V." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasili V." } } ] }, "title": "Stellate Repeats: Targets of Silencing and Modules Causing cis-Inactivation and trans-Activation", "ispublished": "pub", "full_text_status": "restricted", "keywords": "heterochromatic repeats, PEV, retrotransposon, RNA interference, Y chromosome", "note": "\u00a9 2003 Kluwer Academic Publishers. \n\nWe are thankful to C. Tummel for the P[w+] DHR stock. This work was supported by grants from Russian Foundation for Basic Researches (01-04-48514, 00-15-97896, 01-04-06425, 01-04-06426, 01-04-06427, 01-04-06428) and Programs 'Frontiers in Genetics' N 99-1-069.", "abstract": "The mechanism of silencing of testis expressed X-linked Stellate repeats by homologous Y-linked Suppressor of Stellate [Su(Ste)] repeats localized in the crystal locus was studied. The double stranded RNA as a product of symmetrical transcription of Su(Ste) repeat and small iinterfaceSu(Ste) siRNA were revealed suggesting the mechanism of RNA interference (RNAi) for Stellate silencing. The relief of Stellate silencing as a result of impaired complementarity between the sequences of putative target Stellate transcripts and Su(Ste) repeats was shown. The role of RNAi mechanism in the silencing of heterochromatic retrotransposon GATE inserted in Stellate cluster was revealed. The studies of cis-effects of Stellate tandem repeats causing variegated expression of juxtaposed reporter genes were extended and the lacZ variegation in imaginal disc was shown. The exceptional case of a non-variegated expression of mini-white gene juxtaposed to Stellate repeats in a construct inserted into the 39C region was shown to be accompanied by trans-activation in homozygous state. Trans-activation effect was retained after transposition of this construct into heterochromatic environment in spite of strong variegation of a mini-white gene.", "date": "2003-03", "date_type": "published", "publication": "Genetica", "volume": "117", "number": "2-3", "publisher": "Springer", "pagerange": "239-245", "id_number": "CaltechAUTHORS:20190513-133559461", "issn": "0016-6707", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-133559461", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-48514" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "00-15-97896" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06425" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06426" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06427" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06428" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1-069" } ] }, "doi": "10.1023/a:1022952315467", "resource_type": "article", "pub_year": "2003", "author_list": "Gvozdev, Vladimir A.; Aravin, Alexei A.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/n6gfz-wzs27", "eprint_id": 95261, "eprint_status": "archive", "datestamp": "2023-08-19 10:01:03", "lastmod": "2023-10-20 19:03:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "V. V." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "N. M." } }, { "id": "Rozovski\u012d-Ia-M", "name": { "family": "Rozovski\u012d", "given": "Ia. M." } }, { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "M. S." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "[The phenomenon of RNA interference and development of organism]", "ispublished": "pub", "full_text_status": "public", "abstract": "[Article in Russian] \n\nRNA interference consists in specific mRNA degradation in response to introduction of a double-stranded RNA, homologous in nucleotide sequence. RNA interference was found in eukaryotes and is used in genomics as a powerful method to determine the functions of genes with known nucleotide sequences. RNA interference is considered as a tool of protection against viruses and harmful consequences of mobile elements' transposals. The involvement of the components of RNA interference is considered in spermatogenesis of Drosophila melanogaster and regulation of the expression of genes in Caenorhabditis elegans responsible for temporal patterns of development. The role of RNQA interference in stem cell formation and functioning is also considered.", "date": "2002-09", "date_type": "published", "publication": "Ontogenez", "volume": "33", "number": "5", "publisher": "Pleiades Publishing Ltd", "pagerange": "349-360", "id_number": "CaltechAUTHORS:20190506-144851787", "issn": "0475-1450", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190506-144851787", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "resource_type": "article", "pub_year": "2002", "author_list": "Aravin, A. A.; Vagin, V. V.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/8kk20-bhs17", "eprint_id": 95441, "eprint_status": "archive", "datestamp": "2023-08-21 23:06:38", "lastmod": "2023-10-20 20:14:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "M. S." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "V. V." } }, { "id": "Rozovskii-Ya-M", "name": { "family": "Rozovskii", "given": "Ya. M." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "Role of Double-Stranded RNA in Eukaryotic Gene Silencing", "ispublished": "pub", "full_text_status": "restricted", "keywords": "gene expression; RNA interference; posttranscriptional regulation; suppression Drosophila", "note": "\u00a9 2002 MAIK \"Nauka/Interperiodica\". Translated from Molekulyarnaya Biologiya, Vol. 36, No. 2, 2002, pp. 240\u2013251. Original Russian Text Copyright \u00a9 2002 by Aravin, Klenov, Vagin, Rozovskii, Gvozdev. \n\nReceived October 10, 2001. \n\nThis work was supported by the Russian Foundation for Basic Research (project nos. 99-04-48561, 01-04-48514, 00-15-97896, 01-04-06427, 01-04-06428) and the Russian program Frontiers in Genetics (project no. 99-1-069).", "abstract": "Data on RNA interference, that is, posttranscriptional gene silencing by homologous double-stranded (ds) RNA, are reviewed. Gene silencing caused by exogenous dsRNA in artificial systems and observed in transgenic organisms carrying additional gene copies is considered. Data are summarized on the mechanism that arose during evolution of the Drosophila melanogaster genome to suppress repetitive genes with the use of dsRNA and thereby to prevent male sterility. The role of dsRNA in inhibiting expression and transposition of mobile elements is discussed on the basis of authors' own and published findings.", "date": "2002-03", "date_type": "published", "publication": "Molecular Biology", "volume": "36", "number": "2", "publisher": "Springer", "pagerange": "180-188", "id_number": "CaltechAUTHORS:20190513-134220628", "issn": "0026-8933", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-134220628", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "99-04-48561" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-48514" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "00-15-97896" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06427" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-06428" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1-069" } ] }, "doi": "10.1023/a:1015357603566", "resource_type": "article", "pub_year": "2002", "author_list": "Aravin, A. A.; Klenov, M. S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/er8pa-m1e42", "eprint_id": 95442, "eprint_status": "archive", "datestamp": "2023-08-19 07:59:45", "lastmod": "2023-10-20 20:14:17", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "Natalia M." } }, { "id": "Tulin-A-V", "name": { "family": "Tulin", "given": "Alexei V." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "Vasilii V." } }, { "id": "Rozovsky-Ya-M", "name": { "family": "Rozovsky", "given": "Yakov M." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } } ] }, "title": "Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2001 Elsevier Science Ltd. \n\nReceived 15 January 2001, Revised 1 May 2001, Accepted 8 May 2001, Available online 17 July 2001. \n\nWe are grateful to B. McKee for providing unpublished results, S. Bonaccorsi and U. Sch\u00e4fer for fly strains, and Phillip Zamore for RNA size markers. We thank Denis Rebrikov and Sergei Lukyanov for their help with RACE experiments, Thomas Tuschl for advice on the detection of small RNAs, and Alla Kalmykova for critical comments. This work was supported by grants from the Russian Foundation for Basic Researchers (N 99-04-48561, 00-15-97896, and 01-04-48514) and the programs \"Frontiers in Genetics\" (N 99-1-069) and \"Universities to Fundamental Science\".", "abstract": "Background: The injection of double-stranded RNA (dsRNA) has been shown to induce a potent sequence-specific inhibition of gene function in diverse invertebrate and vertebrate species. The homology-dependent posttranscriptional gene silencing (PTGS) caused by the introduction of transgenes in plants may be mediated by dsRNA. The analysis of Caenorhabditis elegans mutants impaired with dsRNA-mediated silencing and studies in plants implicate a biological role of dsRNA-mediated silencing as a transposon-repression and antiviral mechanism.\n\nResults: We investigated the silencing of testis-expressed Stellate genes by paralogous Su(Ste) tandem repeats, which are known to be involved in the maintenance of male fertility in Drosophila melanogaster. We found that both strands of repressor Su(Ste) repeats are transcribed, producing sense and antisense RNA. The Stellate silencing is associated with the presence of short Su(Ste) RNAs. Cotransfection experiments revealed that Su(Ste) dsRNA can target and eliminate Stellate transcripts in Drosophila cell culture. The short fragment of Stellate gene that is homologous to Su(Ste) was shown to be sufficient to confer Su(Ste)-dependent silencing of a reporter construct in testes. We demonstrated that Su(Ste) dsRNA-mediated silencing affects not only Stellate expression but also the level of sense Su(Ste) RNA providing a negative autogenous regulation of Su(Ste) expression. Mutation in the spindle-E gene relieving Stellate silencing also leads to a derepression of the other genomic tandem repeats and retrotransposons in the germline.\n\nConclusions: Homology-dependent gene silencing was shown to be used to inhibit Stellate gene expression in the D. melanogaster germline, ensuring male fertility. dsRNA-mediated silencing may provide a basis for negative autogenous control of gene expression. The related surveillance system is implicated to control expression of retrotransposons in the germline.", "date": "2001-07-10", "date_type": "published", "publication": "Current Biology", "volume": "11", "number": "13", "publisher": "Cell Press", "pagerange": "1017-1027", "id_number": "CaltechAUTHORS:20190513-135711509", "issn": "0960-9822", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-135711509", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "99-04-48561" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "00-15-97896" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "01-04-48514" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1-069" } ] }, "doi": "10.1016/s0960-9822(01)00299-8", "resource_type": "article", "pub_year": "2001", "author_list": "Aravin, Alexei A.; Naumova, Natalia M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/hp3pd-qyb23", "eprint_id": 95443, "eprint_status": "archive", "datestamp": "2023-08-21 22:18:10", "lastmod": "2023-10-20 20:14:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Vagin-V-V", "name": { "family": "Vagin", "given": "V. V." } }, { "id": "Rozovsky-Ya-M", "name": { "family": "Rozovsky", "given": "Ya. M." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "Inhibition of Gene Expression by Homologous Double-Stranded RNA in a Drosophila melanogaster Cell Culture", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Gene Expression; Target Gene; Reporter Gene; Early Development; Specific Inhibition", "note": "\u00a9 2001 MAIK \"Nauka/Interperiodica\". Russian Journal of Genetics, Vol. 37, No. 6, 2001, pp. 639\u2013642. Translated from Genetika, Vol. 37, No. 6, 2001, pp. 779\u2013783. Original Russian Text Copyright \u00a9 2001 by Aravin, Vagin, Rozovsky, Gvozdev. \n\nReceived January 3, 2001. \n\nThis work was supported by the Russian Foundation for Basic Research (project nos. 99-04-48561, 00-15-97896) and the Russian programs \"Frontiers in Genetics\" (project no. 99-1069) and \"Russian Universities: Basic Research\" (project no. 5244).", "abstract": "Specific inhibition of gene expression by exogenous homologous double-stranded RNA (dsRNA) in invertebrates and in the early development of vertebrates is termed RNA interference. Cultured cells were cotransfected with reporter plasmids and dsRNA. The inhibitory effect on reporter gene expression depended on the extent of homology between dsRNA and the target gene. RNA interference was also studied in cells cotransfected with plasmids directing synthesis of sense and antisense RNAs. Production of antisense RNA only slightly inhibited expression of the reporter gene. Simultaneous expression of both sense and antisense RNAs caused by cotransfection by corresponding plasmids did not inhibit expression of the reporter construct.", "date": "2001-06", "date_type": "published", "publication": "Russian Journal of Genetics", "volume": "37", "number": "6", "publisher": "Springer", "pagerange": "639-642", "id_number": "CaltechAUTHORS:20190513-140252620", "issn": "1022-7954", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-140252620", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "99-04-48561" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "00-15-97896" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1069" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "5244" } ] }, "doi": "10.1023/a:1016621207467", "resource_type": "article", "pub_year": "2001", "author_list": "Aravin, A. A.; Vagin, V. V.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/xsz7k-1a484", "eprint_id": 95445, "eprint_status": "archive", "datestamp": "2023-08-21 21:20:59", "lastmod": "2023-10-20 20:14:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } }, { "id": "Kogan-G-L", "name": { "family": "Kogan", "given": "Galina L." } }, { "id": "Tulin-A-A", "name": { "family": "Tulin", "given": "Alexei A." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "Natalia M." } }, { "id": "Shevelyov-Y-Y", "name": { "family": "Shevelyov", "given": "Yury Y." } } ] }, "title": "Paralogous Stellate and Su(Ste) repeats: evolution and ability to silence a reporter gene", "ispublished": "pub", "full_text_status": "restricted", "keywords": "concerted evolution; Stellate repeats; Y chromosome", "note": "\u00a9 2000 Kluwer Academic Publishers. \n\nAccepted 4 June 2000. \n\nThis work was supported by the grants from Russian Foundation of Basic Research (98-04-49107 and 99-04-48561) and Russian Program Frontiers in Genetics (99-1-069).", "abstract": "The X-linked Stellaterepeats, encoding a putative regulatory subunit of protein kinase CK2, are expressed in XO male testes. The Y-linked, testes-expressed paralogous Su(Ste) repeats are thought to be suppressors of Stellatetranscription. The unique, testis-expressed euchromatic gene was suggested to be an ancestor of the both types of amplified paralogous repeats. A Su(Ste)-like orphon was localized on a Y chromosome, outside of the Su(Ste) cluster. Several diagnostic molecular markers peculiar for the both types of diverged Stellateand Su(Ste) units were detected in the orphon sequence. The orphon was suggested to be a close relative of the immediate ancestor of both types of paralogous repeats which initiated evolution on the Y chromosome. Selection pressure on the level of translation was shown as a driving force in the evolution of Su(Ste) repeats, which are considered as more ancient derivatives of the ancestor euchromatic gene than Stellaterepeats. In a vicinity of 12E Stellatecluster the undamaged, recently originated euchromatic Stellateorphon was found at 12D, providing the poly(A) signal for the bendlessgene. P-element mediated transformations reveal that the fragments of cloned Stellateand Su(Ste) clusters are able to induce variegation of a reporter mini-whitegene. The observed variegation phenomenon has peculiar features: a significant increase of trans-activation of a reporter mini-whitegene in homozygous stat; absence of effects of several conventional modifiers of position effect variegation (PEV) and independence of a severity of variegation on a distance between insertion and centromere region.", "date": "2000-07", "date_type": "published", "publication": "Genetica", "volume": "109", "number": "1-2", "publisher": "Springer", "pagerange": "131-140", "id_number": "CaltechAUTHORS:20190513-142605426", "issn": "0016-6707", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-142605426", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research", "grant_number": "98-04-49107" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-04-48561" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1-069" } ] }, "doi": "10.1023/a:1026596419250", "resource_type": "article", "pub_year": "2000", "author_list": "Gvozdev, Vladimir A.; Kogan, Galina L.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/cn1z7-18v43", "eprint_id": 95444, "eprint_status": "archive", "datestamp": "2023-08-19 05:44:10", "lastmod": "2023-10-20 20:14:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kogan-G-L", "name": { "family": "Kogan", "given": "Galina L." } }, { "id": "Epstein-V-N", "name": { "family": "Epstein", "given": "Vitalii N." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexei A." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "Vladimir A." } } ] }, "title": "Molecular Evolution of Two Paralogous Tandemly Repeated Heterochromatic Gene Clusters Linked to the X and Y Chromosomes of Drosophila melanogaster", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2000 by the Society for Molecular Biology and Evolution. \n\nAccepted January 5, 2000. \n\nWe thank Y. Shevelyov for critical comments and V. E. Alatortsev for improvement of the text. We also thank two anonymous reviewers, through whose comments the manuscript was considerably improved. This work was supported by grants from the Russian Foundation of Basic Research (98-04-49107 and 99-04-48561) and the Russian program Frontiers in Genetics (99-1-069).", "abstract": "Here we report the peculiarities of molecular evolution and divergence of paralogous heterochromatic clusters of the testis- expressed X-linked Stellate and Y-linked Su(Ste) tandem repeats. It was suggested that Stellate and Su(Ste) clusters affecting male fertility are the amplified derivatives of the unique euchromatic gene \u03b2CK2tes encoding the putative testis-specific \u03b2-subunit of protein kinase CK2. The putative Su(Ste)-like evolutionary intermediate was detected on the Y chromosome as an orphon outside of the Su(Ste) cluster. The orphon shows extensive homology to the Su(Ste) repeat, but contains several Stellate-like diagnostic nucleotide substitutions, as well as a 10-bp insertion and a 3\u2032 splice site of the first intron typical of the Stellate unit. The orphon looks like a pseudogene carrying a drastically damaged Su(Ste) open reading frame (ORF). The putative Su(Ste) ORF, as compared with the Stellate one, carries numerous synonymous substitutions leading to the major codon preference. We conclude that Su(Ste) ORFs evolved on the Y chromosome under the pressure of translational selection. Direct sequencing shows that the efficiency of concerted evolution between adjacent repeats is 5\u201310 times as high in the Stellate heterochromatic cluster on the X chromosome as that in the Y-linked Su(Ste) cluster, judging by the frequencies of nucleotide substitutions and single-nucleotide deletions.", "date": "2000-05", "date_type": "published", "publication": "Molecular Biology and Evolution", "volume": "17", "number": "5", "publisher": "Oxford University Press", "pagerange": "697-702", "id_number": "CaltechAUTHORS:20190513-141554962", "issn": "1537-1719", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-141554962", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation of Basic Research", "grant_number": "98-04-49107" }, { "agency": "Russian Foundation of Basic Research", "grant_number": "99-04-48561" }, { "agency": "Russian Foundation for Basic Research", "grant_number": "99-1-069" } ] }, "doi": "10.1093/oxfordjournals.molbev.a026348", "resource_type": "article", "pub_year": "2000", "author_list": "Kogan, Galina L.; Epstein, Vitalii N.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/2xw2k-9yh76", "eprint_id": 95262, "eprint_status": "archive", "datestamp": "2023-08-19 05:36:23", "lastmod": "2023-10-20 19:03:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "N. M." } }, { "id": "Tulin-A-V", "name": { "family": "Tulin", "given": "A. V." } }, { "id": "Klenov-M-S", "name": { "family": "Klenov", "given": "M. S." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "[The study of interaction between paralogous tandem repeats stellate and suppressor of stellate in the genome of Drosophila melanogaster]", "ispublished": "pub", "full_text_status": "public", "abstract": "Testis-specific expression of tandemly repeated Stellate genes, located in eu- and heterochromatin regions of the X chromosome of Drosophila melanogaster, is suppressed by homologous Suppressor of Stellate repeats located on the Y chromosome. Using transgenic lines, we have demonstrated that three Su(Ste) copies failed to change the expression of the reporter construction carrying the bacterial beta-galactosidase gene under control of the Stellate gene regulatory sequence. Possible mechanisms of the Su(Ste) repeat suppressor activity are discussed.", "date": "2000-04", "date_type": "published", "publication": "Genetika", "volume": "36", "number": "4", "publisher": "Pleiades Publishing Ltd", "pagerange": "581-584", "id_number": "CaltechAUTHORS:20190506-150001202", "issn": "0016-6758", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190506-150001202", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "resource_type": "article", "pub_year": "2000", "author_list": "Aravin, A. A.; Naumova, N. M.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/w7fep-xc258", "eprint_id": 95263, "eprint_status": "archive", "datestamp": "2023-08-19 03:52:41", "lastmod": "2023-10-20 19:03:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } }, { "id": "Alatortsev-V-E", "name": { "family": "Alatortsev", "given": "V. E." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Kalmykova-A-I", "name": { "family": "Kalmykova", "given": "A. I." } }, { "id": "Kogan-G-L", "name": { "family": "Kogan", "given": "G. L." } }, { "id": "Lavrov-S-A", "name": { "family": "Lavrov", "given": "S. A." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "N. M." } }, { "id": "Nurminski\u012d-D-I", "name": { "family": "Nurminski\u012d", "given": "D. I." } }, { "id": "Rasheva-V-I", "name": { "family": "Rasheva", "given": "V. I." } }, { "id": "Tolchkov-E-V", "name": { "family": "Tolchkov", "given": "E. V." } } ] }, "title": "[Heterochromatin: molecular evolution and effects of gene location in Drosophila melanogaster]", "ispublished": "pub", "full_text_status": "public", "abstract": "[no abstract]", "date": "1999-01", "date_type": "published", "publication": "Molekuliarnaia biologiia", "volume": "33", "number": "1", "publisher": "Izdatelstvo Nauka", "pagerange": "14-25", "id_number": "CaltechAUTHORS:20190506-150344785", "issn": "0026-8984", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190506-150344785", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "resource_type": "article", "pub_year": "1999", "author_list": "Gvozdev, V. A.; Alatortsev, V. E.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1cgs8-fas18", "eprint_id": 95446, "eprint_status": "archive", "datestamp": "2023-08-22 13:01:25", "lastmod": "2023-10-20 20:14:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "Alexey A." } }, { "id": "Yurchenko-V-Yu", "name": { "family": "Yurchenko", "given": "Vyacheslav Yu." } }, { "id": "Merzlyak-E-M", "name": { "family": "Merzlyak", "given": "Ekaterina M." } }, { "id": "Kolesnikov-A-A", "name": { "family": "Kolesnikov", "given": "Alexander A." } } ] }, "title": "The mitochondrial ND8 gene from Crithidia oncopelti is not pan-edited", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Crithidia oncopelti; RNA editing; Maxicircle; ND8", "note": "\u00a9 1998 Federation of European Biochemical Societies. \n\nReceived 17 June 1998. \n\nWe would like to thank Dr. D.A. Maslov for his interest in our work and helpful discussion; Drs. N.S. Entelis, M.N. Merzlyak and I.A. Krascheninnikov for their critical reading of the manuscript and T.A. Yurchenko for her help with pictures. This work was supported by a grant from the Russian Foundation for Basic Research.", "abstract": "RNA editing in trypanosomatid mitochondria is a process involving the insertion and deletion of uridine residues within the coding region of maxicircle messenger RNA transcripts. Twelve of the 17 known genes need editing to produce functional molecules. We have analyzed the predicted editing sites for the Crithidia oncopelti mitochondrial NADH\u2010ubiquinone oxidoreductase subunit 8 (ND8) gene based on known mRNAs from other trypanosomatid species. All studied ND8 mRNAs undergo editing throughout the coding (and 3\u2032 non\u2010coding) sequences (pan\u2010editing). The 5\u2032 part of the C. oncopelti ND8 gene undergoes editing (like in Leishmania tarentolae and Trypanosoma brucei) while the 3\u2032 part of the pre\u2010edited gene corresponds to the 3\u2032 part of edited ND8 mRNAs from other organisms. The organization of the ND8 gene in C. oncopelti mitochondrial DNA differs from all organisms investigated so far \u2013 this gene is not pan\u2010edited. We have also localized the guide RNA for cytochrome b between 9S rRNA and the ND8 gene. This RNA shows high homology to the gCYb\u2010II gene of L. tarentolae and the gCyb gene of Crithidia fasciculata. A hypothetical editing pattern for the cytochrome b gene in C. oncopelti maxicircles is proposed.", "date": "1998-07-24", "date_type": "published", "publication": "FEBS Letters", "volume": "431", "number": "3", "publisher": "Wiley", "pagerange": "457-460", "id_number": "CaltechAUTHORS:20190513-143549674", "issn": "0014-5793", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190513-143549674", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation for Basic Research" } ] }, "doi": "10.1016/s0014-5793(98)00813-8", "resource_type": "article", "pub_year": "1998", "author_list": "Aravin, Alexey A.; Yurchenko, Vyacheslav Yu.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/h1bw9-4n563", "eprint_id": 95362, "eprint_status": "archive", "datestamp": "2023-08-22 12:45:03", "lastmod": "2023-10-20 20:10:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tulin-A-V", "name": { "family": "Tulin", "given": "A. V." } }, { "id": "Naumova-N-M", "name": { "family": "Naumova", "given": "N. M." } }, { "id": "Aravin-A-A", "name": { "family": "Aravin", "given": "A. A." } }, { "id": "Gvozdev-V-A", "name": { "family": "Gvozdev", "given": "V. A." } } ] }, "title": "Repeated, protein-encoding heterochromatic genes cause inactivation of a juxtaposed euchromatic gene", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Heterochromatic repeat; Position effect variegation; Mini-gene white", "note": "\u00a9 1998 Federation of European Biochemical Societies. \n\nReceived 30 January 1998; revised version received 3 February 1998. First published: 14 April 1998. \n\nThe authors thanks Dr. N.G. Shostak for her help in Drosophila germline transformation experiments, Dr. E.G. Pasyukova for detection of the sites of insertions by in situ hybridization and Dr. E. Kurenova for her help to document variations in eye color. This research was supported by the grants from Russian Foundation of Basic Researches (96\u201004\u201049026 and 96\u201015\u201098072) and Russian Program Frontiers in Genetics.", "abstract": "Euchromatic genes are often silenced by rearrangements that place them within or near heterochromatin, a phenomenon known as position effect variegation (PEV). However, little is known about molecular structure of cis\u2010acting heterochromatic fragments responsible for PEV. Here we report that heterochromatic cluster containing Stellate repeats, that encode putative regulatory subunit of protein kinase CK2 cause PEV of a reporter white `mini\u2010gene'. It is the first example of an euchromatic gene being silenced because of the proximity to the natural, well\u2010defined heterochromatic repeat cluster.", "date": "1998-04-03", "date_type": "published", "publication": "FEBS Letters", "volume": "425", "number": "3", "publisher": "Wiley", "pagerange": "513-516", "id_number": "CaltechAUTHORS:20190509-083248818", "issn": "0014-5793", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190509-083248818", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Russian Foundation of Basic Research", "grant_number": "96\u201004\u201049026" }, { "agency": "Russian Foundation of Basic Research", "grant_number": "96\u201015\u201098072" }, { "agency": "Russian Program Frontiers in Genetics" } ] }, "doi": "10.1016/s0014-5793(98)00286-5", "resource_type": "article", "pub_year": "1998", "author_list": "Tulin, A. V.; Naumova, N. M.; et el." } ]