Most studies of emotion have as their subject matter the emotion experiences that people can describe and rate. By contrast to this approach from psychology, studies in animals, and some biological studies in humans, focus on behavior and its adaptive function. These two literatures typically use very different corresponding features by which to characterize emotion: categories or dimensions describing feelings for which we have convenient words, for the former (e.g., happiness, pleasantness), and functional properties for the latter (e.g., persistence, generalizability, approachabil- ity). In this thesis I use both sets of ratings, and I ask whether the latter, biologically inspired features could also be used to characterize people\u2019s emotion experiences, and might reveal novel dimensions of variability. They also typically use different sets of stimuli to induce the emotions: lexical stimuli in which participants are asked to imagine something hypothetical are common in human studies; ecologically valid stimuli that at least the subjects cannot distinguish from the real world are common in animal studies. Here I used three domains of stimuli: stories, videos, and real-life experiences, in the same set of participants, permitting a unique comparison.
\r\n\r\nI took advantage of a sample of approximately 1000 Americans who were surveyed longitudinally over the internet during the COVID-19 pandemic. I collected ratings of emotion experiences evoked by three classes of stimuli: a validated set of short stories, a validated set of short videos, and actual experiences in real life across multiple waves. I found that all three types of emotion experiences could be characterized by low dimensional spaces, with the first two factors that accounted for most of the variance in people\u2019s ratings corresponding to the dimensions of valence and arousal, in line with prior work. However, I discovered additional novel factors related to generalizability (the extent to which an emotion experience is shared across many different situations and occurrences) or modularity (the extent to which an emotion experience is unique to specific situations). The findings show that emotion features not usually assessed in humans can be recovered from subjective ratings of their experiences. I argue for a revision of current dimensional theories of emotion: they have been incomplete because they were restricted to ratings entrenched in how we think of our conscious experience, and the typical English words we use to describe it. The new dimensions validate some theories of emotion and offer hope for linking psychological studies in humans with behavioral or neurobiological work across species. I also characterized the distributions of the three types of emotion experiences and found that emotions were distributed along continuous gradients, with no well-separated clusters even for emotions belonging to the six basic emotion categories.
\r\n\r\nMy thesis presents two additional topics that capitalize on my unique sample: the emotions experienced during the COVID pandemic, and individual differences. For example, I also found that resilience buffered individuals against the effect of loneliness on depression, and that people who had tested positive for COVID felt more morally disgusted towards acts of violating social norms. I also explored the association between psychological traits and differences in emotion experiences both in terms of the magnitudes of the ratings and the overall correlation structure across scales. Again, the richness of my dataset reveals a number of associations that are theoretically interesting and that will be of relevance to understanding mood and anxiety disorders as well.
\r\n\r\nAll of the data will be made publicly available, and the core parts of many of the investigations were pre-registered.
", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:05272022-181044242", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:05272022-181044242", "related_url": { "items": [ { "description": "Article adapted for Chapter 8.", "type": "arxiv", "url": "https://psyarxiv.com/9dac6/" }, { "description": "Article for the dataset.", "type": "arxiv", "url": "https://psyarxiv.com/75eyx/" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "2022-06-03 released PDF after 1-week embargo.", "deposited_by": "Yanting Han", "deposited_on": "2022-05-27 23:29:42", "doi": "10.7907/yhmt-9t69", "divisions": { "items": [ "div_bbe" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "radolphs@hss.caltech.edu", "id": "Adolphs-R", "name": { "family": "Adolphs", "given": "Ralph" }, "orcid": "0000-0002-8053-9692", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "meister@caltech.edu", "id": "Meister-M", "name": { "family": "Meister", "given": "Markus" }, "orcid": "0000-0003-2136-6506", "role": "chair" }, { "email": "fde@caltech.edu", "id": "Eberhardt-F-D", "name": { "family": "Eberhardt", "given": "Frederick D." }, "role": "member" }, { "email": "sshimojo@caltech.edu", "id": "Shimojo-S", "name": { "family": "Shimojo", "given": "Shinsuke" }, "orcid": "0000-0002-1290-5232", "role": "member" }, { "email": "radolphs@hss.caltech.edu", "id": "Adolphs-R", "name": { "family": "Adolphs", "given": "Ralph" }, "orcid": "0000-0002-8053-9692", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2022-05-25", "gradofc_approval_date": "2022-05-27", "review_status": "approved", "option_major": { "items": [ "neurobio" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Han, Yanting" }, { "id": "/id/eprint/14388", "eprint_id": 14388, "rev_number": 56, "documents": [ { "id": "/id/document/135351", "doc_id": 135351, "rev_number": 3, "files": [ { "id": "/id/file/386446", "fileid": 386446, "datasetid": "document", "objectid": 135351, "filename": "Caltech-Thesis_ES_final.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "37dbb63c910cfe8ca323ca340d98d0b7", "hash_type": "MD5", "filesize": 7536744, "mtime": "2021-11-12 23:45:46", "url": "/14388/3/Caltech-Thesis_ES_final.docx" } ], "eprint_id": 14388, "pos": 3, "placement": 3, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "Source files", "language": "en", "security": "internal", "license": "other", "main": "Caltech-Thesis_ES_final.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" }, { "id": "/id/document/135395", "doc_id": 135395, "rev_number": 7, "files": [ { "id": "/id/file/386565", "fileid": 386565, "datasetid": "document", "objectid": 135395, "filename": "Caltech-Thesis_ES_final.pdf", "mime_type": "application/pdf", "hash": "fa04e7213f452e9c248717e7c255bf4e", "hash_type": "MD5", "filesize": 6263040, "mtime": "2021-11-15 19:05:44", "url": "/14388/5/Caltech-Thesis_ES_final.pdf" } ], "eprint_id": 14388, "pos": 5, "placement": 5, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "Full thesis", "language": "en", "security": "public", "license": "other", "main": "Caltech-Thesis_ES_final.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 12678, "dir": "disk0/00/01/43/88", "datestamp": "2021-11-22 18:24:32", "lastmod": "2021-11-30 20:35:49", "status_changed": "2021-11-22 18:24:32", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "emily.savela@gmail.com", "id": "Savela-Emily-Sue", "name": { "family": "Savela", "given": "Emily Sue" }, "orcid": "0000-0001-9614-4276", "show_email": "NO" } ] }, "title": "Nucleic Acid Measurements for Antibiotic Susceptibility Testing and Early Detection of SARS-CoV-2", "ispublished": "unpub", "full_text_status": "public", "keywords": "antibiotic resistance, sexually transmitted infection, diagnostics, antibiotic, Neisseria gonorrhoeae, COVID-19; Saliva; Nasal swab; Diagnostics; Pre-Symptomatic; Surveillance; RT-qPCR; Longitudinal sampling; Case-ascertained; Household study; Transmission", "abstract": "Nucleic-acid-amplification tests (NAATs) are widely used in microbial detection both in environmental characterization and human diagnostics. NAATs offer highly sensitive and specific detection of target molecules among the noise of complex samples. This thesis covers two important applications of nucleic-acid quantification techniques in human clinical samples. First, I co-developed a new phenotypic antibiotic susceptibility test that uses species-specific DNA detection to detect bacterial cell-wall damage following incubation with beta-lactam antibiotics. Second, I helped compile a longitudinal dataset of SARS-CoV-2 viral loads during a community-based COVID-19 study run by the Ismagilov Lab through October 2020 \u2013 April 2021 in the greater Los Angeles County area, USA. Sensitive and specific nucleic-acid tests allowed for robust detection of pathogenic microbes in both these applications. Designing and implementing NAATs for these applications required consideration of biological constraints of the microorganisms, molecular stability over the time of quantification, and the practical constraints of acquiring and transporting samples. Continued innovation of NAAT technologies will be critical to contain present and future pandemics and empower medical professionals with data to inform treatment options.
", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:10072021-173853251", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:10072021-173853251", "related_url": { "items": [ { "description": "Article adapted for Chapter II.", "type": "doi", "url": "https://doi.org/10.1371/journal.pbio.3000651" }, { "description": "Article adapted for Chapter III.", "type": "doi", "url": "https://doi.org/10.1101/2021.04.02.21254771" }, { "description": "Article adapted for Appendix A.", "type": "doi", "url": "https://doi.org/10.1371/journal.pbio.3000652" }, { "description": "Article adapted for Appendix B.", "type": "doi", "url": "https://doi.org/10.1101/2020.12.09.20239467" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Burroughs Wellcome Fund", "grant_number": "IDSEP160030-02" }, { "agency": "Joan and Jerry Doren Fellowship" }, { "agency": "Bill and Melinda Gates Foundation" }, { "agency": "Ronald and Maxine Linde Center for New Initiatives" }, { "agency": "Joseph J. Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Defense Threat Reduction Agency (DTRA)", "grant_number": "MCDC-18-01-01-007" } ] }, "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "Released 2021-11-30 after 1-week embargo // Embargoed for 7 days, ok to release on 11/29/2021", "deposited_by": "Emily Savela", "deposited_on": "2021-11-22 18:24:32", "doi": "10.7907/vp9a-n206", "divisions": { "items": [ "div_bbe" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "rustem@caltech.edu", "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "niles@caltech.edu", "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406", "role": "chair" }, { "email": "dkn@caltech.edu", "id": "Newman-D-K", "name": { "family": "Newman", "given": "Dianne K." }, "orcid": "0000-0003-1647-1918", "role": "member" }, { "email": "jleadbetter@caltech.edu", "id": "Leadbetter-J-R", "name": { "family": "Leadbetter", "given": "Jared R." }, "orcid": "0000-0002-7033-0844", "role": "member" }, { "email": "rustem@caltech.edu", "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2021-10-22", "gradofc_approval_date": "2021-11-19", "review_status": "approved", "option_major": { "items": [ "bioeng" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Savela, Emily Sue" }, { "id": "/id/eprint/14413", "eprint_id": 14413, "rev_number": 96, "documents": [ { "id": "/id/document/135278", "doc_id": 135278, "rev_number": 6, "files": [ { "id": "/id/file/385500", "fileid": 385500, "datasetid": "document", "objectid": 135278, "filename": "hoffmann-magnus_full-embargo-request.pdf", "mime_type": "application/pdf", "hash": "1d5784c1da8c5eef48a2953eabe5863d", "hash_type": "MD5", "filesize": 87042, "mtime": "2021-11-01 17:53:31", "url": "/14413/3/hoffmann-magnus_full-embargo-request.pdf" } ], "eprint_id": 14413, "pos": 3, "placement": 4, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "Author full embargo request 2021-11-01", "language": "en", "security": "internal", "license": "other", "main": "hoffmann-magnus_full-embargo-request.pdf", 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{ "id": "/id/file/385614", "fileid": 385614, "datasetid": "document", "objectid": 135290, "filename": "author request for restriction to campus 20211102.pdf", "mime_type": "application/pdf", "hash": "d04a83b319018ea32247f5739748b3ba", "hash_type": "MD5", "filesize": 435433, "mtime": "2021-11-02 16:07:08", "url": "/14413/6/author request for restriction to campus 20211102.pdf" } ], "eprint_id": 14413, "pos": 6, "placement": 5, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "author-generated downgrade to restriction to campus request 2021-11-02", "language": "en", "security": "internal", "license": "other", "main": "author request for restriction to campus 20211102.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "embargoform" }, { "id": "/id/document/138007", "doc_id": 138007, "rev_number": 5, "files": [ { "id": "/id/file/402496", "fileid": 402496, "datasetid": "document", "objectid": 138007, "filename": "hoffmann-magnus_release-permission.pdf", "mime_type": "application/pdf", "hash": "596f84ad127d99b1e5de15804b76ccba", "hash_type": "MD5", "filesize": 166363, "mtime": "2022-12-07 01:04:03", "url": "/14413/11/hoffmann-magnus_release-permission.pdf" } ], "eprint_id": 14413, "pos": 11, "placement": 2, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "Author and OTTCP approval 2022-12-02", "language": "en", "security": "internal", "license": "other", "main": "hoffmann-magnus_release-permission.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "release" } ], "eprint_status": "archive", "userid": 12680, "dir": "disk0/00/01/44/13", "datestamp": "2021-11-12 20:39:38", "lastmod": "2023-11-08 00:16:02", "status_changed": "2021-11-12 20:39:38", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "magnus.hoffmann@bath.edu", "id": "Hoffmann-Magnus-Adrian-Gero", "name": { "family": "Hoffmann", "given": "Magnus Adrian Gero" }, "orcid": "0000-0003-4923-9568", "show_email": "NO" } ] }, "title": "Nanoparticle Technologies to Cure and Prevent Infectious Diseases", "ispublished": "unpub", "full_text_status": "public", "keywords": "Nanoparticles; HIV-1; gene therapy; vaccines; SARS-CoV-2", "abstract": "Despite almost 40 years of intensive research, there is still no curative treatment for HIV-1/AIDS. Anti-retroviral therapy (ART) prolongs the life expectancy of HIV-1-infected individuals but is associated with side effects, and multiple drugs need to be given in combination to prevent the development of viral resistance. In addition, treatment must continue for the lifetime of the individual due to the existence of a long-lived latent proviral reservoir. While a \"sterilizing\" cure remains difficult to achieve due to difficulties associated with identifying and clearing latently-infected cells, recent research has focused on designing a \"functional\" cure, i.e., a therapeutic strategy that enables long-term suppression of HIV-1 replication and remission of symptoms in the absence of ART. The work presented here describes a new therapeutic direction for the development of a functional cure against HIV-1. This approach is based on the hypothesis that HIV-1 is unable to escape from a nanoparticle (NP)-based decoy that presents clusters of the HIV-1 receptor CD4, because CD4-NPs mimic viral target cells more accurately than soluble CD4-based inhibitors and permit high-avidity interactions with trimeric HIV-1 Env proteins. We demonstrate that CD4-NPs are >10,000-fold more potent than soluble CD4 (sCD4) and prevent viral escape in vitro. AAV-mediated delivery of self-assembling CD4-NPs produced stable CD4-NP serum concentrations in mice that were almost 1,000-fold higher than concentrations required to neutralize HIV-1 in vitro, suggesting that these concentrations could be therapeutic. Viral challenge studies in non-human primates are underway to evaluate the potential of this therapeutic strategy.
\r\n\r\nAs an alternative approach to generate decoys against HIV-1, we generated engineered red blood cells (RBCs) that expressed viral receptors and potently inhibited HIV-1 infection of target cells in vitro. Because RBCs do not contain nuclei or functional organelles required for protein translation, infection of engineered RBCs represents a dead-end for a lentivirus such as HIV-1, which must integrate into the host cell genome as part of its lifecycle. We generated stable erythroid progenitor cell lines that continuously produced HIV-1 receptor-expressing RBCs that could be administered to HIV-1-infected individuals. As RBCs vastly outnumber CD4+ T-cells, HIV-1\u2019s main target cells, and have extended lifetimes, only a fraction of an individual\u2019s RBCs would need to be replaced with the engineered RBC viral traps in order to suppress HIV-1 infection in vivo.
\r\n\r\nMy work on CD4-NP therapeutics against HIV-1 also led to the invention and development of the EBR NP technology that is ideally suited for vaccine design applications. This technology can be used to modify any type of membrane protein to self-assemble into enveloped virus-like NPs without the need for additional proteins. EBR NP assembly is induced by inserting a short amino acid sequence into the cytoplasmic tail of the membrane protein, which was designed to recruit host proteins from the endosomal sorting complex required for transport (ESCRT) pathway. We applied this technology to design protein NP-based vaccines against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which elicited potent serum neutralizing antibody responses in mice. The EBR NP technology is also ideally suited for the development of hybrid vaccine approaches that allow genetic encoding of protein-based NPs, thereby combining attributes of mRNA and protein-based NP vaccines. Pilot studies demonstrated that mRNA and DNA vaccines encoding the self-assembling SARS-CoV-2 spike-EBR construct elicited ~10-fold higher neutralizing antibody responses than mRNA and DNA vaccines encoding the unmodified spike protein. This hybrid approach has the potential to substantially enhance the potency of mRNA vaccines and could become a leading vaccine platform technology. Future applications for the EBR NP technology are discussed, including the development of a universal coronavirus vaccine to prevent future pandemics, and engineering EBR NPs to mRNA vaccines or therapeutic cargoes for efficient and targeted delivery.
", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:10302021-184745797", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:10302021-184745797", "related_url": { "items": [ { "description": "Article adapted for ch. 2", "type": "doi", "url": "https://doi.org/10.1073/pnas.2010320117" }, { "description": "Article adapted for ch. 4", "type": "doi", "url": "https://doi.org/10.1016/j.omtm.2021.03.003" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Bill and Melinda Gates Foundation", "grant_number": "OPP1202246" }, { "agency": "DeLogi Science and Technology Grant" }, { "agency": "Kairos Ventures (Gift)" }, { "agency": "Rothenburg Innovation Initiative" }, { "agency": "Rosen Bioengineering Center (Pilot grant)" }, { "agency": "Center for Environmental Microbiology Interactions (Pilot grant)" } ] }, "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "Released 2023-01-03 with author and OTTCP approval.\r\n\r\n// Withheld until 3 January 2023. OTTCP has a patent pending related to this thesis, and have asked that we continue the embargo until end of calendar year - Kathy 2022-08-08. //\r\n\r\n// Fully withheld until will hear officially from OTTCP; email from Hannah to Kathy indicates that Meimei is waiting to hear back from Magnus as of 2021-11-08//\r\n\r\n\r\n// Restriction to campus until 02 May 2022 - author has spoken to OTTCP who advised that restriction to campus would be good enough - SKJ 20211102. Was originally scheduled to be Withheld until 2022-05-02 // From author: My thesis contains details about a technology that I invented as a PhD student in Pamela Bjorkman's laboratory. We have filed a provisional patent application for this technology: Hoffmann MAG, Bjorkman PJ (2021). Self-assembling viral spike-EBR nanoparticles as a vaccine platform technology. US Patent Application No. 63/208,889. US Patent and Trademark Office. We would like to request a full embargo as this technology is subject to ongoing negotiations about licensing agreements with potential industrial partners.", "deposited_by": "Magnus Hoffmann", "deposited_on": "2021-11-12 20:39:38", "doi": "10.7907/g0w1-rc77", "divisions": { "items": [ "div_bbe" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "sarkis@caltech.edu", "id": "Mazmanian-S-K", "name": { "family": "Mazmanian", "given": "Sarkis K." }, "orcid": "0000-0003-2713-1513", "role": "chair" }, { "email": "niles@caltech.edu", "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406", "role": "member" }, { "email": "baltimo@caltech.edu", "id": "Baltimore-D-L", "name": { "family": "Baltimore", "given": "David L." }, "orcid": "0000-0001-8723-8190", "role": "member" }, { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2021-10-26", "gradofc_approval_date": "2021-11-12", "thesis_awards": "Milton and Francis Clauser Doctoral Prize, 2022.\r\nLawrence L. and Audrey W. Ferguson Prize, 2022.", "review_status": "approved", "option_major": { "items": [ "biology" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Hoffmann, Magnus Adrian Gero" }, { "id": "/id/eprint/14487", "eprint_id": 14487, "rev_number": 25, "documents": [ { "id": "/id/document/135925", "doc_id": 135925, "rev_number": 6, "files": [ { "id": "/id/file/389232", "fileid": 389232, "datasetid": "document", "objectid": 135925, "filename": "Abernathy-Thesis-020121.pdf", "mime_type": "application/pdf", "hash": "dfcfa45e3f3456a5ec3804eee31efe1b", "hash_type": "MD5", "filesize": 26146429, "mtime": "2022-02-01 19:19:17", "url": "/14487/1/Abernathy-Thesis-020121.pdf" } ], "eprint_id": 14487, "pos": 1, "placement": 1, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "Original deposit. KJ deleted blank pages p.xi-xii, p.[287] (last page) in replacement copy / skj 2022-02-01", "language": "en", "security": "internal", "license": "other", "main": "Abernathy-Thesis-020121.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" }, { "id": "/id/document/135926", "doc_id": 135926, "rev_number": 3, "files": [ { "id": "/id/file/389234", "fileid": 389234, "datasetid": "document", "objectid": 135926, "filename": "Abernathy-Thesis-020121.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "63158da4b97c1952974a0e2bbce50204", "hash_type": "MD5", "filesize": 25754483, "mtime": "2022-02-01 19:19:58", "url": "/14487/2/Abernathy-Thesis-020121.docx" } ], "eprint_id": 14487, "pos": 2, "placement": 2, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "source file", "language": "en", "security": "internal", "license": "other", "main": "Abernathy-Thesis-020121.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" }, { "id": "/id/document/135929", "doc_id": 135929, "rev_number": 4, "files": [ { "id": "/id/file/389245", "fileid": 389245, "datasetid": "document", "objectid": 135929, "filename": "Abernathy-Thesis-020121-r.pdf", "mime_type": "application/pdf", "hash": "f6f6f9c9c53e3a61a39943c429d354f8", "hash_type": "MD5", "filesize": 26075626, "mtime": "2022-02-01 20:07:52", "url": "/14487/5/Abernathy-Thesis-020121-r.pdf" } ], "eprint_id": 14487, "pos": 5, "placement": 5, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "Abernathy-Thesis-020121-r.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 12667, "dir": "disk0/00/01/44/87", "datestamp": "2022-03-11 23:57:53", "lastmod": "2023-11-08 00:16:02", "status_changed": "2022-03-11 23:57:53", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "morgan.abernathy481@gmail.com", "id": "Abernathy-Morgan-Elizabeth", "name": { "family": "Abernathy", "given": "Morgan Elizabeth" }, "orcid": "0000-0001-9959-7713", "show_email": "NO" } ] }, "title": "Antibody Targeting of HIV-1 Env: a Structural Perspective", "ispublished": "unpub", "full_text_status": "public", "keywords": "broadly neutralizing antibody, HIV-1, SARS-CoV-2, cryo-EM", "abstract": "A key component of contemporary efforts toward a human immunodeficiency virus 1 (HIV-1) vaccine is the use of structural biology to understand the structural characteristics of antibodies elicited both from human patients and animals immunized with engineered 'immunogens,' or early vaccine candidates. This thesis will report on projects characterizing both types of antibodies against HIV-1. Chapter 1 will introduce relevant topics, including the reasons HIV-1 is particularly capable of evading the immune system in natural infection and after vaccination, the 20+ year history of unsuccessful HIV-1 vaccine large-scale efficacy trials, an introduction to broadly neutralizing antibodies (bNAbs), and a review of common strategies utilized in HIV-1 immunogen design today. Chapter 2 describes the isolation, high-resolution structural characterization, and in vitro resistance profile of a new bNAb, 1-18, that is both very broad and potent, as well as able to restrict HIV-1 escape in vivo. Chapter 3 reports the results of an epitope-focusing immunogen design and immunization experiment carried out in wild type mice, rabbits, and non-human primates where it was shown that B cells targeting the desired epitope were expanded after a single prime immunization with immunogen RC1 or a variant, RC1-4fill. Chapter 4 describes Ab1245, an off-target non-neutralizing monoclonal antibody isolated in a macaque that had been immunized with a series of sequential immunogens after the prime immunization reported in Chapter 3. The antibody structure describes a specific type of distracting response as it binds in a way that causes a large structural change in Env, resulting in the destruction of the neutralizing fusion peptide epitope. Chapter 5 is adapted from a review about how antibodies differentially recognize the viruses HIV-1, SARS-CoV-2, and Zika virus. This review serves as an introduction to the virus SARS-CoV-2, which is the topic of the final chapter, Chapter 6. In this chapter, structures of many neutralizing antibodies isolated from SARS-CoV-2 patients were used to define potentially therapeutic classes of neutralizing receptor-binding domain (RBD) antibodies based on their epitopes and binding profiles.", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:02012022-191225421", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:02012022-191225421", "related_url": { "items": [ { "description": "Article adapted for ch. 2", "type": "doi", "url": "https://doi.org/10.1016/j.cell.2020.01.010" }, { "description": "Article adapted for ch. 3", "type": "doi", "url": "https://doi.org/10.1038/s41586-019-1250-z" }, { "description": "Article adapted for ch. 4", "type": "doi", "url": "https://doi.org/10.1038/s41541-021-00387-4" }, { "description": "Article adapted for ch. 5", "type": "doi", "url": "https://doi.org/10.3390/v13102106" }, { "description": "Article adapted for ch. 6", "type": "doi", "url": "https://doi.org/10.1038/s41586-020-2852-1" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "collection": "CaltechTHESIS", "reviewer": "Kathy Johnson", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "2022-03-18 released after 1-week embargo.", "deposited_by": "Morgan Abernathy", "deposited_on": "2022-03-11 23:57:53", "doi": "10.7907/0p2b-aa45", "divisions": { "items": [ "div_chem" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "dcrees@caltech.edu", "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185", "role": "chair" }, { "email": "tirrell@caltech.edu", "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596", "role": "member" }, { "email": "clemons@caltech.edu", "id": "Clemons-W-M", "name": { "family": "Clemons", "given": "William M." }, "orcid": "0000-0002-0021-889X", "role": "member" }, { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2021-12-03", "gradofc_approval_date": "2022-03-11", "review_status": "approved", "option_major": { "items": [ "chemistry" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Abernathy, Morgan Elizabeth" }, { "id": "/id/eprint/14302", "eprint_id": 14302, "rev_number": 43, "documents": [ { "id": "/id/document/134554", "doc_id": 134554, "rev_number": 4, "files": [ { "id": "/id/file/380736", "fileid": 380736, "datasetid": "document", "objectid": 134554, "filename": "Thesis Stephen Grant Final_v2.pdf", "mime_type": "application/pdf", "hash": "6748ea9eb05dc099ce615de6791570f7", "hash_type": "MD5", "filesize": 6628490, "mtime": "2021-07-14 23:56:05", "url": "/14302/1/Thesis Stephen Grant Final_v2.pdf" } ], "eprint_id": 14302, "pos": 1, "placement": 1, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "Thesis Stephen Grant Final_v2.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" }, { "id": "/id/document/134556", "doc_id": 134556, "rev_number": 3, "files": [ { "id": "/id/file/380741", "fileid": 380741, "datasetid": "document", "objectid": 134556, "filename": "Thesis Source Files.zip", "mime_type": "application/zip", "hash": "2c76f6ac389180ecc1122b478bc3d847", "hash_type": "MD5", "filesize": 25185094, "mtime": "2021-07-14 23:57:22", "url": "/14302/2/Thesis Source Files.zip" } ], "eprint_id": 14302, "pos": 2, "placement": 2, "mime_type": "application/zip", "format": "application/zip", "format_desc": "Source Files", "language": "en", "security": "internal", "license": "other", "main": "Thesis Source Files.zip", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" } ], "eprint_status": "archive", "userid": 10742, "dir": "disk0/00/01/43/02", "datestamp": "2021-07-27 20:49:00", "lastmod": "2022-07-13 22:32:56", "status_changed": "2021-07-27 20:49:00", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "stephen.grant@alumni.stonybrook.edu", "id": "Grant-Stephen-Nicholas", "name": { "family": "Grant", "given": "Stephen Nicholas" }, "orcid": "0000-0003-0923-8886", "show_email": "YES" } ] }, "title": "Investigation of Some Small Molecule-Protein and Protein-Protein Interactions in Nicotine Addiction, Opioid Use Disorder, and COVID-19", "ispublished": "unpub", "full_text_status": "public", "keywords": "COVID-19, opioid use disorder, nicotine addiction, neuroscience, electrophysiology, microscopy", "abstract": "Nicotine addiction, opioid use disorder, and COVID-19 have made lasting impacts on every aspect of society. These are complicated conditions, and studies in these fields will likely continue for decades, if not centuries. Here, we make contributions to each of these issues using electrophysiology and microscopy. The first chapter goes into the motivation behind this thesis and the major experiments I used in my graduate career. In the second chapter, we introduce a new amino acid into the mouse muscle nicotinic acetylcholine receptor in an attempt to understand the dynamics of receptor activation. In the third chapter, we continue the Lester lab\u2019s work on the neuroscientific effects of menthol and how it plays a role in nicotine addiction. We found the binding site for menthol on the \u03b14\u03b22 nicotinic acetylcholine receptor, which continues our hypothesis that the neuroscientific effects of menthol are detrimental to cigarette smokers. Fortunately, partly because of our studies, mentholated nicotine products are being phased out of the United States. The fourth and fifth chapters investigate \u03bc-opioid receptor trafficking, both the trafficking from the endoplasmic reticulum and endocytosis from the plasma membrane. Both of these events play a role in inducing opioid use disorder and increasing the danger of using opioids. We hope that these studies will help other researchers understand opioid use disorder and fight the opioid epidemic. Finally, we studied the effects of SARS-COV-2 proteins on epithelial sodium channels. These channels are important for regulating lung fluid levels where their improper function may cause pulmonary edema. Pulmonary edema has been observed in COVID-19 patients. Altogether, we believe that we have made meaningful impacts on these important health concerns in this thesis. We look forward to how the scientific communities continue to build on our results.
", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:07142021-175425546", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:07142021-175425546", "related_url": { "items": [ { "description": "Article adapted for Chapter 3.", "type": "doi", "url": "https://doi.org/10.1523/eneuro.0465-18.2018" }, { "description": "Article adapted for Chapter 6.", "type": "doi", "url": "https://doi.org/10.1016/j.bpj.2021.06.005" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "National Institute of Drug Abuse", "grant_number": "DA046122" } ] }, "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "deposited_by": "Stephen Grant", "deposited_on": "2021-07-27 20:49:00", "doi": "10.7907/pdtj-8238", "divisions": { "items": [ "div_chem" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "lester@caltech.edu", "id": "Lester-H-A", "name": { "family": "Lester", "given": "Henry A." }, "orcid": "0000-0002-5470-5255", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "tirrell@caltech.edu", "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596", "role": "chair" }, { "email": "jkbarton@caltech.edu", "id": "Barton-J-K", "name": { "family": "Barton", "given": "Jacqueline K." }, "orcid": "0000-0001-9883-1600", "role": "member" }, { "email": "dadougherty@caltech.edu", "id": "Dougherty-D-A", "name": { "family": "Dougherty", "given": "Dennis A." }, "orcid": "0000-0003-1464-2461", "role": "member" }, { "email": "lester@caltech.edu", "id": "Lester-H-A", "name": { "family": "Lester", "given": "Henry A." }, "orcid": "0000-0002-5470-5255", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2021-07-12", "gradofc_approval_date": "2021-07-27", "review_status": "approved", "option_major": { "items": [ "chemistry" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Grant, Stephen Nicholas" }, { "id": "/id/eprint/14550", "eprint_id": 14550, "rev_number": 47, "documents": [ { "id": "/id/document/136222", "doc_id": 136222, "rev_number": 2, "files": [ { "id": "/id/file/390866", "fileid": 390866, "datasetid": "document", "objectid": 136222, "filename": "Gu_Alan_PhD Thesis final 20220418.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "6f51397ddb341a62d56ced92e52eb657", "hash_type": "MD5", "filesize": 11449591, "mtime": "2022-04-19 16:29:30", "url": "/14550/1/Gu_Alan_PhD Thesis final 20220418.docx" } ], "eprint_id": 14550, "pos": 1, "placement": 1, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "source file", "language": "en", "security": "internal", "license": "other", "main": "Gu_Alan_PhD Thesis final 20220418.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" }, { "id": "/id/document/136223", "doc_id": 136223, "rev_number": 4, "files": [ { "id": "/id/file/390868", "fileid": 390868, "datasetid": "document", "objectid": 136223, "filename": "Gu_Alan_PhD Thesis final 20220418.pdf", "mime_type": "application/pdf", "hash": "27b746f7216d6f9573642a37af9573d3", "hash_type": "MD5", "filesize": 5584311, "mtime": "2022-04-19 16:29:36", "url": "/14550/2/Gu_Alan_PhD Thesis final 20220418.pdf" } ], "eprint_id": 14550, "pos": 2, "placement": 2, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "Gu_Alan_PhD Thesis final 20220418.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 11406, "dir": "disk0/00/01/45/50", "datestamp": "2022-04-20 19:42:16", "lastmod": "2025-02-04 23:41:07", "status_changed": "2022-04-20 19:42:16", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "alan.on.ca@gmail.com", "id": "Gu-Alan-Yalun", "name": { "family": "Gu", "given": "Alan Yalun" }, "orcid": "0000-0001-8095-3634", "show_email": "NO" } ] }, "title": "Aqueous Aerosols in Atmospheric Chemistry and Airborne Diseases", "ispublished": "unpub", "full_text_status": "public", "keywords": "Aerosol Interface Atmosphere SARS-CoV-2", "abstract": "Aqueous atmospheric aerosols are small droplets (typically smaller than 5 \u03bcm) suspended in the air that are comprised of water and water-soluble components. These aerosols provide an air-water interfacial reaction environment on their surfaces, and act as a medium for airborne disease transmission. In this thesis, Chapters II and V explore atmospherically relevant reactions on the aqueous aerosol surface using an online mass spectrometry, while Chapter III investigates the SARS-CoV-2 airborne transmission considering suspended virus-laden aerosols as the transmission media. Spinning off this SARS-CoV-2 work, Chapter IV describes a newly developed quantitative RNA amplification test kit for COVID-19, with an emphasis on the amplification result photo recognition component.", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:04142022-025410011", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:04142022-025410011", "related_url": { "items": [ { "description": "Article adapted for ch. 2: Role of Ferryl Ion Intermediates in Fast Fenton Chemistry on Aqueous Microdroplets", "type": "doi", "url": "https://pubs.acs.org/doi/10.1021/acs.est.1c01962" }, { "description": "Article adapted for ch. 3: Speech-Generated Aerosol Settling Times and Viral Viability Can Improve COVID-19 Transmission Prediction", "type": "doi", "url": "https://pubs.rsc.org/en/Content/ArticleLanding/2022/EA/D1EA00013F" }, { "description": "Article adapted for ch. 4: Membrane-Based In-Gel Loop-Mediated Isothermal Amplification (mgLAMP) System for SARS-CoV-2 Quantification in Environmental Waters", "type": "doi", "url": "https://pubs.acs.org/doi/10.1021/acs.est.1c04623" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "AGS-1744353" }, { "agency": "Bill & Melinda Gates Foundation", "grant_number": "OPP1192379, INV-018569, and INV-030223" }, { "agency": "Resnick Sustainability Institute", "grant_number": "SRA" } ] }, "collection": "CaltechTHESIS", "reviewer": "Kathy Johnson", "local_group": { "items": [ "COVID-19", "Resnick Sustainability Institute" ] }, "suggestions": "2022-04-27 file released after 1-week embargo expired.", "deposited_by": "Alan Gu", "deposited_on": "2022-04-20 19:42:16", "doi": "10.7907/4spy-az88", "divisions": { "items": [ "div_chem" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "mrh@caltech.edu", "id": "Hoffmann-M-R", "name": { "family": "Hoffmann", "given": "Michael R." }, "orcid": "0000-0001-6495-1946", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "wennberg@caltech.edu", "id": "Wennberg-P-O", "name": { "family": "Wennberg", "given": "Paul O." }, "orcid": "0000-0002-6126-3854", "role": "chair" }, { "email": "hbgray@caltech.edu", "id": "Gray-H-B", "name": { "family": "Gray", "given": "Harry B." }, "orcid": "0000-0002-7937-7876", "role": "member" }, { "email": "wag@caltech.edu", "id": "Goddard-W-A-III", "name": { "family": "Goddard", "given": "William A., III" }, "orcid": "0000-0003-0097-5716", "role": "member" }, { "email": "mrh@caltech.edu", "id": "Hoffmann-M-R", "name": { "family": "Hoffmann", "given": "Michael R." }, "orcid": "0000-0001-6495-1946", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2022-04-07", "gradofc_approval_date": "2022-04-19", "thesis_awards": "Demetriades-Tsafka-Kokkalis Prize in Entrepreneurship or Related Fields, 2022.", "review_status": "approved", "option_major": { "items": [ "chemeng" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Gu, Alan Yalun" }, { "id": "/id/eprint/14565", "eprint_id": 14565, "rev_number": 27, "documents": [ { "id": "/id/document/136248", "doc_id": 136248, "rev_number": 3, "files": [ { "id": "/id/file/391121", "fileid": 391121, "datasetid": "document", "objectid": 136248, "filename": "jette_claudia_2022_thesis.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "8ddf2fccc9d14c657f19eaa97d690068", "hash_type": "MD5", "filesize": 99231443, "mtime": "2022-04-28 19:50:30", "url": "/14565/1/jette_claudia_2022_thesis.docx" } ], "eprint_id": 14565, "pos": 1, "placement": 1, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "source file for .pdf", "language": "en", "security": "internal", "license": "cc_by_nc", "main": "jette_claudia_2022_thesis.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "updated" }, { "id": "/id/document/136250", "doc_id": 136250, "rev_number": 5, "files": [ { "id": "/id/file/391127", "fileid": 391127, "datasetid": "document", "objectid": 136250, "filename": "jette_claudia_2022_thesis.pdf", "mime_type": "application/pdf", "hash": "76289e06fd04a1739443984bd9de5479", "hash_type": "MD5", "filesize": 57758294, "mtime": "2022-04-28 20:26:52", "url": "/14565/2/jette_claudia_2022_thesis.pdf" } ], "eprint_id": 14565, "pos": 2, "placement": 2, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "jette_claudia_2022_thesis.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 12796, "dir": "disk0/00/01/45/65", "datestamp": "2022-05-03 20:35:04", "lastmod": "2023-11-08 00:16:02", "status_changed": "2022-05-03 20:35:04", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "akie.jette@gmail.com", "id": "Jette-Claudia-Angela", "name": { "family": "Jette", "given": "Claudia Angela" }, "orcid": "0000-0002-5085-8027", "show_email": "NO" } ] }, "title": "Targeting Fusion Proteins of HIV-1 and SARS-CoV-2", "ispublished": "unpub", "full_text_status": "public", "keywords": "structural biology, viruses, HIV-1, SARS-CoV-2, COVID-19, antibody, small molecule, peptide, cryo-EM, X-ray crystallography, protein", "abstract": "Viruses are disease-causing pathogenic agents that require host cells to replicate. Fusion of host and viral membranes is critical for the lifecycle of enveloped viruses. Studying viral fusion proteins can allow us to better understand how they shape immune responses and inform the design of therapeutics such as drugs, monoclonal antibodies, and vaccines. This thesis discusses two approaches to targeting two fusion proteins: Env from HIV-1 and S from SARS-CoV-2. The first chapter of this thesis is an introduction to viruses with a specific focus on HIV-1 CD4 mimetic drugs and antibodies against SARS-CoV-2. It discusses the architecture of these viruses and fusion proteins and how small molecules, peptides, and antibodies can target these proteins successfully to treat and prevent disease. In addition, a brief overview is included of the techniques involved in structural biology and how it has informed the study of viruses. For the interested reader, chapter 2 contains a review article that serves as a more in-depth introduction for both viruses as well as how the use of structural biology has informed the study of viral surface proteins and neutralizing antibody responses to them. The subsequent chapters provide a body of work divided into two parts. The first part in chapter 3 involves a study on conformational changes induced in the HIV-1 Env protein by CD4-mimemtic drugs using single particle cryo-EM. The second part encompassing chapters 4 and 5 includes two studies on antibodies isolated from convalescent COVID-19 donors. The former involves classification of antibody responses to the SARS-CoV-2 S receptor-binding domain (RBD). The latter discusses an anti-RBD antibody class that binds to a conserved epitope on the RBD and shows cross-binding and cross-neutralization to other coronaviruses in the sarbecovirus subgenus.
", "date": "2022", "date_type": "degree", "id_number": "CaltechThesis:04282022-192922044", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechThesis:04282022-192922044", "related_url": { "items": [ { "description": "Article adapted for Chapter 3", "type": "doi", "url": "http://www.doi.org/10.1038/s41467-021-21816-x" }, { "description": "Article adapted for Chapter 4", "type": "doi", "url": "http://www.doi.org/10.1038/s41586-020-2852-1" }, { "description": "Article adapted for Chapter 5", "type": "doi", "url": "http://www.doi.org/10.1016/j.celrep.2021.109760" }, { "description": "Article adapted for Chapter 2", "type": "doi", "url": "http://www.doi.org/10.3390/v13102106" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "2022-05-10 released after 1-week embargo expired.", "deposited_by": "Claudia Jette", "deposited_on": "2022-05-03 20:35:04", "doi": "10.7907/pxa2-dy41", "divisions": { "items": [ "div_chem" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "clemons@caltech.edu", "id": "Clemons-W-M", "name": { "family": "Clemons", "given": "William M." }, "orcid": "0000-0002-0021-889X", "role": "chair" }, { "email": "voorhees@caltech.edu", "id": "Voorhees-R-M", "name": { "family": "Voorhees", "given": "Rebecca M." }, "orcid": "0000-0003-1640-2293", "role": "member" }, { "email": "baltimore@caltech.edu", "id": "Baltimore-D-L", "name": { "family": "Baltimore", "given": "David L." }, "orcid": "0000-0001-8723-8190", "role": "member" }, { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2022-04-06", "gradofc_approval_date": "2022-05-03", "review_status": "approved", "option_major": { "items": [ "biochem" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Jette, Claudia Angela" }, { "id": "/id/eprint/14592", "eprint_id": 14592, "rev_number": 42, "documents": [ { "id": "/id/document/136441", "doc_id": 136441, "rev_number": 6, "files": [ { "id": "/id/file/392128", "fileid": 392128, "datasetid": "document", "objectid": 136441, "filename": "Esswein_Shannon_PhD_thesis_submitted.pdf", "mime_type": "application/pdf", "hash": "40527fbabbdc02c18d970f492d36657e", "hash_type": "MD5", "filesize": 10577822, "mtime": "2022-05-21 23:00:03", "url": "/14592/6/Esswein_Shannon_PhD_thesis_submitted.pdf" } ], "eprint_id": 14592, "pos": 6, "placement": 2, "mime_type": "application/pdf", "format": "application/pdf", "format_desc": "Reduced file size", "language": "en", "security": "public", "license": "other", "main": "Esswein_Shannon_PhD_thesis_submitted.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" }, { "id": "/id/document/136619", "doc_id": 136619, "rev_number": 4, "files": [ { "id": "/id/file/392973", "fileid": 392973, "datasetid": "document", "objectid": 136619, "filename": "thesis_draft13.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "72961c4a60a0cd0b7c12a270c2c463b6", "hash_type": "MD5", "filesize": 644519412, "mtime": "2022-05-25 23:33:41", "url": "/14592/8/thesis_draft13.docx" } ], "eprint_id": 14592, "pos": 8, "placement": 3, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "MS Word version of thesis", "language": "en", "security": "internal", "license": "other", "main": "thesis_draft13.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" }, { "id": "/id/document/136621", "doc_id": 136621, "rev_number": 5, "files": [ { "id": "/id/file/392981", "fileid": 392981, "datasetid": "document", "objectid": 136621, "filename": "thesis_draft13.pdf", "mime_type": "application/pdf", "hash": "da8823ea662f12371c08960b886b59f4", "hash_type": "MD5", "filesize": 290818840, "mtime": "2022-05-25 23:45:32", "url": "/14592/9/thesis_draft13.pdf" } ], "eprint_id": 14592, "pos": 9, "placement": 1, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "thesis_draft13.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 12808, "dir": "disk0/00/01/45/92", "datestamp": "2022-05-24 19:11:10", "lastmod": "2023-11-08 00:16:02", "status_changed": "2022-05-24 19:11:10", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "sesswein@g.ucla.edu", "id": "Esswein-Shannon-Rose", "name": { "family": "Esswein", "given": "Shannon Rose" }, "orcid": "0000-0002-5142-0190", "show_email": "NO" } ] }, "title": "Structural Basis of Antibody Recognition of Viruses", "ispublished": "unpub", "full_text_status": "public", "keywords": "Zika; flavivirus; coronavirus; immunology; neutralizing antibodies; structural biology, cryo-electron microscopy, X-ray crystallography", "abstract": "The Zika epidemic in 2015-2016 and COVID-19 pandemic in 2019-2021 are the latest reminders of the enormous impact of viruses on the world. Zika, a flavivirus transmitted by mosquitos, can cause severe neurodevelopmental abnormalities including microcephaly in the newborns of the infected mothers. Vaccine design is complicated by concern that elicited antibodies may also recognize other epidemic-causing flaviviruses that share a similar envelope protein, such as dengue virus, West Nile Virus, and yellow fever virus. This cross-reactivity, if non-neutralizing, may worsen symptoms of a subsequent infection through antibody-dependent enhancement (ADE). To better understand the neutralizing antibody response and risk of ADE, we compared germline and mature antibody binding to Zika and other flaviviruses. We showed that affinity maturation of the light chain variable domain is important for strong binding of VH3-23/VK1-5 neutralizing antibodies to Zika virus envelope domain III (EDIII) and identified interactions that contribute to weak, cross-reactive binding to West Nile Virus EDIII. These findings informed our design of EDIII-conjugated mosaic nanoparticles as a pan-flavivirus vaccine candidate. Sera from immunization trials with nanoparticles displaying EDIIIs of Zika and dengue serotypes 1-4 showed cross-reactive binding to Zika, dengue 1-4, and West Nile Virus, a promising step towards the development of safe and effective flavivirus vaccines.
\r\n\r\nCoronaviruses are another group of viruses responsible for widespread morbidity and mortality, including the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemics and current SARS-CoV-2 pandemic. Given concerns regarding new SARS-CoV-2 variants and the possibility for additional zoonotic betacoronaviruses to cause future outbreaks, we investigated how the epitopes on the SARS-CoV-2 receptor binding domain (RBD) targeted by VH3-30-derived antibodies correlate with their neutralization potency and breadth of betacoronavirus recognition. Analyses showed how variations in antibody light chains and CDRH3 lengths facilitate the diverse RBD epitopes, cross-reactivity, and neutralization profiles of VH3-30 Abs, illustrating their importance for vaccine design and therapeutic antibody development.
", "date": "2022", "date_type": "degree", "id_number": "CaltechTHESIS:05202022-005152490", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:05202022-005152490", "related_url": { "items": [ { "description": "Article adapted for Chapter 2", "type": "doi", "url": "https://doi.org/10.1073/pnas.1919269117" }, { "description": "Article related to content in Chapter 5.", "type": "doi", "url": "https://doi.org/10.1038/s41586-020-2852-1" }, { "description": "Article related to content in Chapter 2.", "type": "doi", "url": "https://doi.org/10.1073/pnas.2000414117" }, { "description": "Article related to content in Chapters 1-5.", "type": "doi", "url": "https://doi.org/10.3390/v13102106" } ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P01AI138938" }, { "agency": "NIH", "grant_number": "5-T32-GM007616-40" }, { "agency": "NIH", "grant_number": "F30AI147579" }, { "agency": "NIH", "grant_number": "T32-GM008042" } ] }, "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "suggestions": "1-week embargo expires 2022-05-31.", "deposited_by": "Shannon Esswein", "deposited_on": "2022-05-24 19:11:10", "doi": "10.7907/krjp-se81", "divisions": { "items": [ "div_chem" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "advisor" } ] }, "thesis_committee": { "items": [ { "email": "dcrees@caltech.edu", "id": "Rees-D-C", "name": { "family": "Rees", "given": "Douglas C." }, "orcid": "0000-0003-4073-1185", "role": "chair" }, { "email": "vorphan@gps.caltech.edu", "id": "Orphan-V-J", "name": { "family": "Orphan", "given": "Victoria J." }, "orcid": "0000-0002-5374-6178", "role": "member" }, { "email": "tirrell@caltech.edu", "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596", "role": "member" }, { "email": "bjorkman@caltech.edu", "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2021-07-14", "gradofc_approval_date": "2022-05-24", "thesis_awards": "NIH NIAID F30 MD-PhD Pre-doctoral Fellowship, Josephine de Karman Dissertation Fellowship, Chen Graduate Innovator Award", "review_status": "approved", "option_major": { "items": [ "biochem" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2022", "author_list": "Esswein, Shannon Rose" }, { "id": "/id/eprint/14073", "eprint_id": 14073, "rev_number": 30, "documents": [ { "id": "/id/document/114351", "doc_id": 114351, "rev_number": 3, "files": [ { "id": "/id/file/350718", "fileid": 350718, "datasetid": "document", "objectid": 114351, "filename": "20210203_Thesis Consolidated_Banerjee.docx", "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "hash": "abd4bfcfc1ecb7686936111d9c08c056", "hash_type": "MD5", "filesize": 56529628, "mtime": "2021-02-03 18:36:32", "url": "/14073/1/20210203_Thesis Consolidated_Banerjee.docx" } ], "eprint_id": 14073, "pos": 1, "placement": 1, "mime_type": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "format": "application/msword", "format_desc": "source file - Complete Thesis (.docx format)", "language": "en", "security": "internal", "license": "other", "main": "20210203_Thesis Consolidated_Banerjee.docx", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "archival" }, { "id": "/id/document/114352", "doc_id": 114352, "rev_number": 4, "files": [ { "id": "/id/file/350720", "fileid": 350720, "datasetid": "document", "objectid": 114352, "filename": "20210203_Thesis Consolidated_Banerjee.pdf", "mime_type": "application/pdf", "hash": "17f9e13a5f2399f0e84cd0eb7b5e2290", "hash_type": "MD5", "filesize": 33191471, "mtime": "2021-02-03 18:39:34", "url": "/14073/2/20210203_Thesis Consolidated_Banerjee.pdf" } ], "eprint_id": 14073, "pos": 2, "placement": 2, "mime_type": "application/pdf", "format": "application/pdf", "language": "en", "security": "public", "license": "other", "main": "20210203_Thesis Consolidated_Banerjee.pdf", "media_duration": "0", "media_aspect_ratio": "0", "media_sample_start": "0", "media_sample_stop": "0", "content": "final" } ], "eprint_status": "archive", "userid": 12468, "dir": "disk0/00/01/40/73", "datestamp": "2021-02-12 23:30:46", "lastmod": "2021-10-26 20:38:42", "status_changed": "2021-02-12 23:30:46", "type": "thesis", "metadata_visibility": "show", "creators": { "items": [ { "email": "abhik.kumar.banerjee@gmail.com", "id": "Banerjee-Abhik-Kumar", "name": { "family": "Banerjee", "given": "Abhik Kumar" }, "orcid": "0000-0002-9797-0104", "show_email": "NO" } ] }, "title": "Diverse Roles of RNA-protein Interactions: From Viral Antagonism to Mammalian Development", "ispublished": "unpub", "full_text_status": "public", "keywords": "RNA-protein interactions, SARS-CoV-2, Kcnq1ot1, Spen, SHARP, Covalent Linkage Affinity Purification ; COVID-19", "abstract": "RNA is a widely utilized and integrated component of core cellular function because of its abilities to recognize and hybridize to nucleic acid templates, spatially localize to different compartments within the cell, bind combinatorially to effector molecules, and in some cases directly catalyze chemical reactions. In this thesis, I describe three cases, illustrating the biomolecule\u2019s unique importance in several different aspects of cellular homeostasis. Chapter 1 provides historical context for studying RNA-protein interactions within RNA biology and Virology. Chapter 2 details experiments in which we explored RNA as a central target of host cell takeover by SARS-CoV-2. In the process, we highlight the importance of RNA in many integral complexes within the cell, including components of the spliceosome, the eukaryotic ribosome, and signal recognition particle. Chapter 3 presents data from our consideration of RNA within the context of cis gene regulation. We specifically focus on a model RNA-binding protein, SMRT/HDAC1 Associated Repressor Protein (SHARP), and the paternally imprinted long non-coding RNA, Kcnq1ot1, as case studies. Chapter 4 describes our dissection of a transcriptional circuit involving SHARP and discusses implications of RNA-binding to developmentally sensitive circuits and processes. Finally, Chapter 5 poses new questions raised by these studies. Together these data emphasize the diverse and unique role RNA plays in cellular homeostasis and suggest additional roles in nuclear compartment stabilization and crosstalk.
", "date": "2021", "date_type": "degree", "id_number": "CaltechTHESIS:02032021-180657616", "refereed": "FALSE", "official_url": "https://resolver.caltech.edu/CaltechTHESIS:02032021-180657616", "related_url": { "items": [ { "description": "Article adapted for Chapter 2.", "type": "doi", "url": "https://doi.org/10.1016/j.cell.2020.10.004" }, { "description": "Article adapted for Chapter 3.", "type": "doi", "url": "https://doi.org/10.1101/2020.08.25.267435" }, { "description": "Article adapted for Chapter 3.", "type": "doi", "url": "https://doi.org/10.1101/2020.11.22.393546" } ] }, "referencetext": { "items": [ "Chapter 1:\r\n\r\n1. Dahm R. (2005). Friedrich Miescher and the discovery of DNA.\u00a0Developmental biology,\u00a0278(2), 274\u2013288. https://doi.org/10.1016/j.ydbio.2004.11.028\r\n\r\n2. Jarroux, J., Morillon, A., and Pinskaya, M. (2017). History, Discovery, and Classification of lncRNAs.\u00a0Advances in experimental medicine and biology,\u00a01008, 1\u201346. https://doi.org/10.1007/978-981-10-5203-3_1\r\n\r\n3. Levene, P.A. (1910). On the biochemistry of nucleic acids. Journal of the American Chemical Society, 32(2), 231-240. https://pubs.acs.org/doi/abs/10.1021/ja01920a010\r\n\r\n4. Frixione, E., and Ruiz-Zamarripa, L. (2019). The \"scientific catastrophe\" in nucleic acids research that boosted molecular biology.\u00a0The Journal of biological chemistry,\u00a0294(7), 2249\u20132255. https://doi.org/10.1074/jbc.CL119.007397\r\n\r\n5. Ochoa, S. (1980). The pursuit of a hobby.\u00a0Annual review of biochemistry,\u00a049, 1\u201330. https://doi.org/10.1146/annurev.bi.49.070180.000245\r\n\r\n6. Griffiths, A.J., Miller, J.H., Suzuki, D.T., et al. (2000). An Introduction to Genetic Analysis. 7th Edition, W.H. Freeman. Transcription and RNA polymerase. Available from: https://\r\nwww.ncbi.nlm.nih.gov/books/NBK22085/\r\n\r\n7. Franklin, R.E., and Gosling, R.G. (2003). Molecular configuration in sodium thymonucleate. 1953.\u00a0Nature,\u00a0421(6921), 400\u2013396.\r\n\r\n8. Crick, F.H. (1958). On protein synthesis.\u00a0Symposia of the Society for Experimental Biology,\u00a012, 138\u2013163.\r\n\r\n9. Crick, F. (1970). Central dogma of molecular biology.\u00a0Nature,\u00a0227(5258), 561\u2013563. https://doi.org/10.1038/227561a0\r\n\r\n10. Cobb, M. (2015). Who discovered messenger RNA?.\u00a0Current biology : CB,\u00a025(13), R526\u2013R532. https://doi.org/10.1016/j.cub.2015.05.032\r\n\r\n11. Palade, G.E. (1955). A small particulate component of the cytoplasm.\u00a0The Journal of biophysical and biochemical cytology,\u00a01(1), 59\u201368. https://doi.org/10.1083/jcb.1.1.59\r\n\r\n12. Berk A.J. (2016). Discovery of RNA splicing and genes in pieces.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0113(4), 801\u2013805. https://doi.org/10.1073/pnas.1525084113\r\n\r\n13. Weinberg, R.A., and Penman, S. (1968). Small molecular weight monodisperse nuclear RNA.\u00a0Journal of molecular biology,\u00a038(3), 289\u2013304. https://doi.org/10.1016/0022-2836(68)90387-2\r\n\r\n14. Zieve, G., and Penman, S. (1976). Small RNA species of the HeLa cell: metabolism and subcellular localization.\u00a0Cell,\u00a08(1), 19\u201331. https://doi.org/10.1016/0092-8674(76)90181-1\r\n\r\n15. Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.\u00a0Cell,\u00a075(5), 843\u2013854. https://doi.org/10.1016/0092-8674(93)90529-y\r\n\r\n16. Wightman, B., Ha, I., and Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.\u00a0Cell,\u00a075(5), 855\u2013862. https://doi.org/10.1016/0092-8674(93)90530-4\r\n\r\n17. Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., and Mello, C.C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.\u00a0Nature,\u00a0391(6669), 806\u2013811. https://doi.org/10.1038/35888\r\n\r\n18. Pachnis, V., Belayew, A., and Tilghman, S.M. (1984). Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a081(17), 5523\u20135527. https://doi.org/10.1073/pnas.81.17.5523\r\n\r\n19. Bartolomei, M.S., Zemel, S., and Tilghman, S.M. (1991). Parental imprinting of the mouse H19 gene.\u00a0Nature,\u00a0351(6322), 153\u2013155. https://doi.org/10.1038/351153a0\r\n\r\n20. Borsani, G., Tonlorenzi, R., Simmler, M. C., Dandolo, L., Arnaud, D., Capra, V., Grompe, M., Pizzuti, A., Muzny, D., Lawrence, C., Willard, H.F., Avner, P., and Ballabio, A. (1991). Characterization of a murine gene expressed from the inactive X chromosome.\u00a0Nature,\u00a0351(6324), 325\u2013329. https://doi.org/10.1038/351325a0\r\n\r\n21. Strehle, M., and Guttman, M. (2020). Xist drives spatial compartmentalization of DNA and protein to orchestrate initiation and maintenance of X inactivation.\u00a0Current opinion in cell biology,\u00a064, 139\u2013147. https://doi.org/10.1016/j.ceb.2020.04.009\u2028\u202822. \r\n\r\n22. Hoagland, M.B., Keller, E.B., and Zamecnik, P.C. (2009). The mechanism of amino acid activation: the work of Mahlon Hoagland. 1956.\u00a0The Journal of biological chemistry,\u00a0284(25), e7\u2013e8.\u2028\u202823.\r\n\r\n23. Hoagland, M.B., Stephenson, M.L., Scott, J.F., Hecht, L.I., and Zamecnik, P.C. (1958). A soluble ribonucleic acid intermediate in protein synthesis.\u00a0The Journal of biological chemistry,\u00a0231(1), 241\u2013257.\u2028\r\n\r\n24. Inouye, M., and Delihas, N. (1988). Small RNAs in the prokaryotes: a growing list of diverse roles.\u00a0Cell,\u00a053(1), 5\u20137. https://doi.org/10.1016/0092-8674(88)90480-1\r\n\r\n25. Okazaki, Y., Furuno, M., Kasukawa, T., Adachi, J., Bono, H., Kondo, S., Nikaido, I., Osato, N., Saito, R., Suzuki, H., Yamanaka, I., Kiyosawa, H., Yagi, K., Tomaru, Y., Hasegawa, Y., Nogami, A., Sch\u00f6nbach, C., Gojobori, T., Baldarelli, R., Hill, D.P., \u2026 RIKEN Genome Exploration Research Group Phase I and II Team (2002). Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.\u00a0Nature,\u00a0420(6915), 563\u2013573. https://doi.org/10.1038/nature01266\r\n\r\n26. Kapranov, P., Cheng, J., Dike, S., Nix, D.A., Duttagupta, R., Willingham, A.T., Stadler, P. F., Hertel, J., Hackerm\u00fcller, J., Hofacker, I.L., Bell, I., Cheung, E., Drenkow, J., Dumais, E., Patel, S., Helt, G., Ganesh, M., Ghosh, S., Piccolboni, A., Sementchenko, V., \u2026 Gingeras, T.R. (2007). RNA maps reveal new RNA classes and a possible function for pervasive transcription.\u00a0Science (New York, N.Y.),\u00a0316(5830), 1484\u20131488. https://doi.org/10.1126/science.1138341\r\n\r\n27. Engreitz, J.M., Haines, J.E., Perez, E.M., Munson, G., Chen, J., Kane, M., McDonel, P.E., Guttman, M., and Lander, E.S. (2016). Local regulation of gene expression by lncRNA promoters, transcription and splicing.\u00a0Nature,\u00a0539(7629), 452\u2013455. https://doi.org/10.1038/nature20149\r\n\r\n28. Hon, C.C., Ramilowski, J.A., Harshbarger, J., Bertin, N., Rackham, O.J., Gough, J., Denisenko, E., Schmeier, S., Poulsen, T. M., Severin, J., Lizio, M., Kawaji, H., Kasukawa, T., Itoh, M., Burroughs, A.M., Noma, S., Djebali, S., Alam, T., Medvedeva, Y.A., Testa, A.C., \u2026 Forrest, A. R. (2017). An atlas of human long non-coding RNAs with accurate 5' ends.\u00a0Nature,\u00a0543(7644), 199\u2013204. https://doi.org/10.1038/nature21374\r\n\r\n29. Ali, T., and Grote, P. (2020). Beyond the RNA-dependent function of LncRNA genes.\u00a0eLife,\u00a09, e60583. https://doi.org/10.7554/eLife.60583\r\n\r\n30. ENCODE Project Consortium, Birney, E., Stamatoyannopoulos, J.A., Dutta, A., Guig\u00f3, R., Gingeras, T.R., Margulies, E.H., Weng, Z., Snyder, M., Dermitzakis, E.T., Thurman, R.E., Kuehn, M.S., Taylor, C.M., Neph, S., Koch, C.M., Asthana, S., Malhotra, A., Adzhubei, I., Greenbaum, J.A., Andrews, R. M., \u2026 de Jong, P.J. (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.\u00a0Nature,\u00a0447(7146), 799\u2013816. https://doi.org/10.1038/nature05874\r\n\r\n31. ENCODE Project Consortium (2012). An integrated encyclopedia of DNA elements in the human genome.\u00a0Nature,\u00a0489(7414), 57\u201374. https://doi.org/10.1038/nature11247\r\n\r\n32. Bassett, A. R., Akhtar, A., Barlow, D.P., Bird, A.P., Brockdorff, N., Duboule, D., Ephrussi, A., Ferguson-Smith, A.C., Gingeras, T.R., Haerty, W., Higgs, D.R., Miska, E.A., and Ponting, C. P. (2014). Considerations when investigating lncRNA function in vivo.\u00a0eLife,\u00a03, e03058. https://doi.org/10.7554/eLife.03058\r\n\r\n33. Paralkar, V.R., Mishra, T., Luan, J., Yao, Y., Kossenkov, A.V., Anderson, S.M., Dunagin, M., Pimkin, M., Gore, M., Sun, D., Konuthula, N., Raj, A., An, X., Mohandas, N., Bodine, D. M., Hardison, R.C., and Weiss, M.J. (2014). Lineage and species-specific long noncoding RNAs during erythro-megakaryocytic development.\u00a0Blood,\u00a0123(12), 1927\u20131937. https://doi.org/10.1182/blood-2013-12-544494\r\n\r\n34. Paralkar, V.R., Taborda, C.C., Huang, P., Yao, Y., Kossenkov, A.V., Prasad, R., Luan, J., Davies, J.O., Hughes, J.R., Hardison, R.C., Blobel, G.A., and Weiss, M.J. (2016). Unlinking an lncRNA from Its Associated cis Element.\u00a0Molecular cell,\u00a062(1), 104\u2013110. https://doi.org/10.1016/j.molcel.2016.02.029\r\n\r\n35. Groff, A.F., Sanchez-Gomez, D.B., Soruco, M., Gerhardinger, C., Barutcu, A.R., Li, E., Elcavage, L., Plana, O., Sanchez, L.V., Lee, J.C., Sauvageau, M., and Rinn, J.L. (2016). In\u00a0Vivo Characterization of Linc-p21 Reveals Functional cis-Regulatory DNA Elements.\u00a0Cell reports,\u00a016(8), 2178\u20132186. https://doi.org/10.1016/j.celrep.2016.07.050\r\n\r\n36. Sauvageau, M., Goff, L.A., Lodato, S., Bonev, B., Groff, A.F., Gerhardinger, C., Sanchez-Gomez, D.B., Hacisuleyman, E., Li, E., Spence, M., Liapis, S.C., Mallard, W., Morse, M., Swerdel, M.R., D'Ecclessis, M.F., Moore, J.C., Lai, V., Gong, G., Yancopoulos, G.D., Frendewey, D., \u2026 Rinn, J.L. (2013). Multiple knockout mouse models reveal lincRNAs are required for life and brain development.\u00a0eLife,\u00a02, e01749. https://doi.org/10.7554/eLife.01749\r\n\r\n37. Goff, L.A., Groff, A.F., Sauvageau, M., Trayes-Gibson, Z., Sanchez-Gomez, D.B., Morse, M., Martin, R.D., Elcavage, L.E., Liapis, S.C., Gonzalez-Celeiro, M., Plana, O., Li, E., Gerhardinger, C., Tomassy, G.S., Arlotta, P., and Rinn, J.L. (2015). Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0112(22), 6855\u20136862. https://doi.org/10.1073/pnas.1411263112\r\n\r\n38. Furlan, G., Gutierrez Hernandez, N., Huret, C., Galupa, R., van Bemmel, J.G., Romito, A., Heard, E., Morey, C., and Rougeulle, C. (2018). The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products.\u00a0Molecular cell,\u00a070(3), 462\u2013472.e8. https://doi.org/10.1016/j.molcel.2018.03.024\r\n\r\n39. Chureau, C., Chantalat, S., Romito, A., Galvani, A., Duret, L., Avner, P., and Rougeulle, C. (2011). Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region.\u00a0Human molecular genetics,\u00a020(4), 705\u2013718. https://doi.org/10.1093/hmg/ddq516\r\n\r\n40. Ebisuya, M., Yamamoto, T., Nakajima, M., and Nishida, E. (2008). Ripples from neighbouring transcription.\u00a0Nature cell biology,\u00a010(9), 1106\u20131113. https://doi.org/10.1038/ncb1771\r\n\r\n41. Fattahi, S., Kosari-Monfared, M., Golpour, M., Emami, Z., Ghasemiyan, M., Nouri, M., and Akhavan-Niaki, H. (2020). LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine.\u00a0Journal of cellular physiology,\u00a0235(4), 3189\u20133206. https://doi.org/10.1002/jcp.29260\r\n\r\n42. Galamb, O., Bart\u00e1k, B.K., Kalm\u00e1r, A., Nagy, Z.B., Szigeti, K.A., Tulassay, Z., Igaz, P., and Moln\u00e1r, B. (2019). Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors.\u00a0World journal of gastroenterology,\u00a025(34), 5026\u20135048. https://doi.org/10.3748/wjg.v25.i34.5026\r\n\r\n43. Dastmalchi, N., Safaralizadeh, R., and Nargesi, M.M. (2020). LncRNAs: Potential Novel Prognostic and Diagnostic Biomarkers in Colorectal Cancer.\u00a0Current medicinal chemistry,\u00a027(30), 5067\u20135077. https://doi.org/10.2174/0929867326666190227230024\r\n\r\n44. Kino, T., Hurt, D.E., Ichijo, T., Nader, N., and Chrousos, G.P. (2010). Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor.\u00a0Science signaling,\u00a03(107), ra8. https://doi.org/10.1126/scisignal.2000568\r\n\r\n45. Poliseno, L., and Pandolfi, P.P. (2015). PTEN ceRNA networks in human cancer.\u00a0Methods (San Diego, Calif.),\u00a077-78, 41\u201350. https://doi.org/10.1016/j.ymeth.2015.01.013\r\n\r\n46. Guo, X., Deng, L., Deng, K., Wang, H., Shan, T., Zhou, H., Liang, Z., Xia, J., and Li, C. (2016). Pseudogene PTENP1 Suppresses Gastric Cancer Progression by Modulating PTEN.\u00a0Anti-cancer agents in medicinal chemistry,\u00a016(4), 456\u2013464. https://doi.org/10.2174/1871520615666150507121407\r\n\r\n47. An, Y., Furber, K.L., and Ji, S. (2017). Pseudogenes regulate parental gene expression via ceRNA network.\u00a0Journal of cellular and molecular medicine,\u00a021(1), 185\u2013192. https://doi.org/10.1111/jcmm.12952\r\n\r\n48. Hu, G., Niu, F., Humburg, B.A., Liao, K., Bendi, S., Callen, S., Fox, H. S., and Buch, S. (2018). Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis.\u00a0Oncotarget,\u00a09(26), 18648\u201318663. https://doi.org/10.18632/oncotarget.24307\r\n\r\n49. Bass, B.L., and Cech, T.R. (1984). Specific interaction between the self-splicing RNA of Tetrahymena and its guanosine substrate: implications for biological catalysis by RNA.\u00a0Nature,\u00a0308(5962), 820\u2013826. https://doi.org/10.1038/308820a0\r\n\r\n50. Kruger, K., Grabowski, P. J., Zaug, A.J., Sands, J., Gottschling, D.E., and Cech, T.R. (1982). Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena.\u00a0Cell,\u00a031(1), 147\u2013157. https://doi.org/10.1016/0092-8674(82)90414-7\r\n\r\n51. Cech, T.R., and Steitz, J.A. (2014). The noncoding RNA revolution-trashing old rules to forge new ones.\u00a0Cell,\u00a0157(1), 77\u201394. https://doi.org/10.1016/j.cell.2014.03.008\r\n\r\n52. Cech T.R. (1990). Nobel lecture. Self-splicing and enzymatic activity of an intervening sequence RNA from Tetrahymena.\u00a0Bioscience reports,\u00a010(3), 239\u2013261. https://doi.org/10.1007/BF01117241\r\n\r\n53. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N., and Altman, S. (1983). The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme.\u00a0Cell,\u00a035(3 Pt 2), 849\u2013857. https://doi.org/10.1016/0092-8674(83)90117-4\r\n\r\n54. Wu, S., Mao, G., and Kirsebom, L.A. (2016). Inhibition of Bacterial RNase P RNA by Phenothiazine Derivatives.\u00a0Biomolecules,\u00a06(3), 38. https://doi.org/10.3390/biom6030038\r\n\r\n55. Brimacombe, R., and Stiege, W. (1985). Structure and function of ribosomal RNA.\u00a0The Biochemical journal,\u00a0229(1), 1\u201317. https://doi.org/10.1042/bj2290001\r\n\r\n56. Noller, H.F., Hoffarth, V., and Zimniak, L. (1992). Unusual resistance of peptidyl transferase to protein extraction procedures.\u00a0Science (New York, N.Y.),\u00a0256(5062), 1416\u20131419. https://doi.org/10.1126/science.1604315\r\n\r\n57. Voorhees, R.M., and Ramakrishnan, V. (2013). Structural basis of the translational elongation cycle.\u00a0Annual review of biochemistry,\u00a082, 203\u2013236. https://doi.org/10.1146/annurev-biochem-113009-092313\r\n\r\n58. Quinodoz, S., and Guttman, M. (2014). Long noncoding RNAs: an emerging link between gene regulation and nuclear organization.\u00a0Trends in cell biology,\u00a024(11), 651\u2013663. https://doi.org/10.1016/j.tcb.2014.08.009\r\n\r\n59. Tycowski, K. T., Shu, M.D., Kukoyi, A., and Steitz, J.A. (2009). A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles.\u00a0Molecular cell,\u00a034(1), 47\u201357. https://doi.org/10.1016/j.molcel.2009.02.020\r\n\r\n60. Venteicher, A.S., Abreu, E.B., Meng, Z., McCann, K.E., Terns, R.M., Veenstra, T.D., Terns, M.P., and Artandi, S.E. (2009). A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.\u00a0Science (New York, N.Y.),\u00a0323(5914), 644\u2013648. https://doi.org/10.1126/science.1165357\r\n\r\n61. Egan, E.D., and Collins, K. (2010). Specificity and stoichiometry of subunit interactions in the human telomerase holoenzyme assembled in vivo.\u00a0Molecular and cellular biology,\u00a030(11), 2775\u20132786. https://doi.org/10.1128/MCB.00151-10\r\n\r\n62. McHugh, C.A., Chen, C. K., Chow, A., Surka, C. F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M. J., Shishkin, A.A., Su, J., Lander, E.S., Hess, S., Plath, K., and Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.\u00a0Nature,\u00a0521(7551), 232\u2013236. https://doi.org/10.1038/nature14443\r\n\r\n63. Chu, C., Zhang, Q.C., da Rocha, S.T., Flynn, R.A., Bharadwaj, M., Calabrese, J.M., Magnuson, T., Heard, E., and Chang, H.Y. (2015). Systematic discovery of Xist RNA binding proteins.\u00a0Cell,\u00a0161(2), 404\u2013416. https://doi.org/10.1016/j.cell.2015.03.025\r\n\r\n64. Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T.B., and Brockdorff, N. (2015). A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.\u00a0Cell reports,\u00a012(4), 562\u2013572. https://doi.org/10.1016/j.celrep.2015.06.053\r\n\r\n65. Monfort, A., Di Minin, G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., and Wutz, A. (2015). Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.\u00a0Cell reports,\u00a012(4), 554\u2013561. https://doi.org/10.1016/j.celrep.2015.06.067\r\n\r\n66. Chen, C. K., Blanco, M., Jackson, C., Aznauryan, E., Ollikainen, N., Surka, C., Chow, A., Cerase, A., McDonel, P., and Guttman, M. (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing.\u00a0Science (New York, N.Y.),\u00a0354(6311), 468\u2013472. https://doi.org/10.1126/science.aae0047\r\n\r\n67. Wutz, A., and Jaenisch, R. (2000). A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation.\u00a0Molecular cell,\u00a05(4), 695\u2013705. https://doi.org/10.1016/s1097-2765(00)80248-8\r\n\r\n68. Peritz, T., Zeng, F., Kannanayakal, T. J., Kilk, K., Eir\u00edksd\u00f3ttir, E., Langel, U., and Eberwine, J. (2006). Immunoprecipitation of mRNA-protein complexes.\u00a0Nature protocols,\u00a01(2), 577\u2013580. https://doi.org/10.1038/nprot.2006.82\r\n\r\n69. Keene, J.D., Komisarow, J.M., and Friedersdorf, M.B. (2006). RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts.\u00a0Nature protocols,\u00a01(1), 302\u2013307. https://doi.org/10.1038/nprot.2006.47\r\n\r\n70. Hendrickson, G.D., Kelley, D.R., Tenen, D., Bernstein, B., and Rinn, J.L. (2016). Widespread RNA binding by chromatin-associated proteins.\u00a0Genome biology,\u00a017, 28. https://doi.org/10.1186/s13059-016-0878-3\r\n\r\n71. Darnell R.B. (2010). HITS-CLIP: panoramic views of protein-RNA regulation in living cells.\u00a0Wiley interdisciplinary reviews. RNA,\u00a01(2), 266\u2013286. https://doi.org/10.1002/wrna.31\r\n\r\n72. Garcin E.D. (2019). GAPDH as a model non-canonical AU-rich RNA binding protein.\u00a0Seminars in cell and developmental biology,\u00a086, 162\u2013173. https://doi.org/10.1016/j.semcdb.2018.03.013\r\n\r\n73. Sigova, A.A., Abraham, B.J., Ji, X., Molinie, B., Hannett, N.M., Guo, Y. E., Jangi, M., Giallourakis, C.C., Sharp, P.A., and Young, R.A. (2015). Transcription factor trapping by RNA in gene regulatory elements.\u00a0Science (New York, N.Y.),\u00a0350(6263), 978\u2013981. https://doi.org/10.1126/science.aad3346\r\n\r\n74. Mili, S., and Steitz, J.A. (2004). Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses.\u00a0RNA (New York, N.Y.),\u00a010(11), 1692\u20131694. https://doi.org/10.1261/rna.7151404\r\n\r\n75. Zhao, J., Sun, B.K., Erwin, J.A., Song, J.J., and Lee, J.T. (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.\u00a0Science (New York, N.Y.),\u00a0322(5902), 750\u2013756. https://doi.org/10.1126/science.1163045\r\n\r\n76. Cifuentes-Rojas, C., Hernandez, A.J., Sarma, K., and Lee, J.T. (2014). Regulatory interactions between RNA and polycomb repressive complex 2.\u00a0Molecular cell,\u00a055(2), 171\u2013185. https://doi.org/10.1016/j.molcel.2014.05.009\r\n\r\n77. Schoeftner, S., Sengupta, A.K., Kubicek, S., Mechtler, K., Spahn, L., Koseki, H., Jenuwein, T., and Wutz, A. (2006). Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing.\u00a0The EMBO journal,\u00a025(13), 3110\u20133122. https://doi.org/10.1038/sj.emboj.7601187\r\n\r\n78. Kalantry, S., and Magnuson, T. (2006). The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation.\u00a0PLoS genetics,\u00a02(5), e66. https://doi.org/10.1371/journal.pgen.0020066\r\n\r\n79. Plath, K., Fang, J., Mlynarczyk-Evans, S.K., Cao, R., Worringer, K.A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., and Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation.\u00a0Science (New York, N.Y.),\u00a0300(5616), 131\u2013135. https://doi.org/10.1126/science.1084274\r\n\r\n80. da Rocha, S. T., Boeva, V., Escamilla-Del-Arenal, M., Ancelin, K., Granier, C., Matias, N. R., Sanulli, S., Chow, J., Schulz, E., Picard, C., Kaneko, S., Helin, K., Reinberg, D., Stewart, A. F., Wutz, A., Margueron, R., and Heard, E. (2014). Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.\u00a0Molecular cell,\u00a053(2), 301\u2013316. https://doi.org/10.1016/j.molcel.2014.01.002\r\n\r\n81. Kohlmaier, A., Savarese, F., Lachner, M., Martens, J., Jenuwein, T., and Wutz, A. (2004). A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.\u00a0PLoS biology,\u00a02(7), E171. https://doi.org/10.1371/journal.pbio.0020171\r\n\r\n82. Portoso, M., Ragazzini, R., Bren\u010di\u010d, \u017d., Moiani, A., Michaud, A., Vassilev, I., Wassef, M., Servant, N., Sargueil, B., and Margueron, R. (2017). PRC2 is dispensable for\u00a0HOTAIR-mediated transcriptional repression.\u00a0The EMBO journal,\u00a036(8), 981\u2013994. https://doi.org/10.15252/embj.201695335\r\n\r\n83. Brockdorff, N. (2013). Noncoding RNA and Polycomb recruitment.\u00a0RNA (New York, N.Y.),\u00a019(4), 429\u2013442. https://doi.org/10.1261/rna.037598.112\r\n\r\n84. Enquist, L. W., and Editors of the Journal of Virology (2009). Virology in the 21st century.\u00a0Journal of virology,\u00a083(11), 5296\u20135308. https://doi.org/10.1128/JVI.00151-09\r\n\r\n85. Volkin, E., and Astrachan, L. (1956). Phosphorus incorporation in Escherichia coli ribo-nucleic acid after infection with bacteriophage T2.\u00a0Virology,\u00a02(2), 149\u2013161. https://doi.org/10.1016/0042-6822(56)90016-2\r\n\r\n86. Brenner, S., Jacob, F., and Meselson, M. (1961). An unstable intermediate carrying information from genes to ribosomes for protein synthesis.\u00a0Nature,\u00a0190, 576\u2013581. https://doi.org/10.1038/190576a0\r\n\r\n87. Fraenkel-Conrat, H. (1956). The role of the nucleic acid in the reconstitution of active tobacco mosaic virus. Journal of the American Chemical Society, 78(4), 882-883. https://doi.org/10.1021/ja01585a055\r\n\r\n88. Temin, H.M., and Mizutani, S. (1970). Viral RNA-dependent DNA Polymerase: RNA-dependent DNA Polymerase in Virions of Rous Sarcoma Virus. Nature, 226, 1211-1213. https://www.nature.com/articles/2261211a0\r\n\r\n89. Baltimore, D. (1970). Viral RNA-dependent DNA Polymerase: RNA-dependent DNA Polymerase in Virions of RNA Tumour Viruses. Nature, 226, 1209-1211.\u2028\u202890. Lavi, S., and Shatkin, A.J. (1975). Methylated simian virus 40 specific RNA from nuclei and cytoplasm of infected BSC 1 cells. Proceedings of the National Academy of Sciences of the United States of America, 72(6), 2012-2016.\r\n\r\n91. Wei, C.M., and Moss, B. (1975). Methylated nucleotides block 5' terminus of vaccinia virus messenger RNA. Proceedings of the National Academy of Sciences of the United States of America, 72(1), 318-322.\r\n\r\n\u202892. Chow, L.T., Roberts, J.M., Lewis, J.B., and Broker, T.R. (1977). A map of cytoplasmic RNA transcripts from lytic adenovirus type 2, determined by electron microscopy of RNA:DNA hybrids.\u00a0Cell,\u00a011(4), 819\u2013836. https://doi.org/10.1016/0092-8674(77)90294-x\r\n\r\n93. Berk, A.J., and Sharp, P.A. (1977). Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids.\u00a0Cell,\u00a012(3), 721\u2013732. https://doi.org/10.1016/0092-8674(77)90272-0\r\n\r\n94. Berget, S.M., Moore, C., and Sharp, P.A. (1977). Spliced segments at the 5\u2032 terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences of the United States of America, 74(8), 3171-3175. https://doi.org/10.1073/pnas.74.8.3171\r\n\r\n95. Berk A.J. (2016). Discovery of RNA splicing and genes in pieces.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0113(4), 801\u2013805. https://doi.org/10.1073/pnas.1525084113\r\n\r\n96. Fitzgerald, M., and Shenk, T. (1981). The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs.\u00a0Cell,\u00a024(1), 251\u2013260. https://doi.org/10.1016/0092-8674(81)90521-3\r\n\r\n97. Napoli, C., Lemieux, C., and Jorgensen, R. (1990). Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans.\u00a0The Plant cell,\u00a02(4), 279\u2013289. https://doi.org/10.1105/tpc.2.4.279\r\n\r\n98. Angell, S.M., and Baulcombe, D.C. (1997). Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA.\u00a0The EMBO journal,\u00a016(12), 3675\u20133684. https://doi.org/10.1093/emboj/16.12.3675\r\n\r\n99. Ratcliff, F., Harrison, B.D., and Baulcombe, D.C. (1997). A similarity between viral defense and gene silencing in plants.\u00a0Science (New York, N.Y.),\u00a0276(5318), 1558\u20131560. https://doi.org/10.1126/science.276.5318.1558\r\n\r\n100. Eamens, A., Wang, M.B., Smith, N.A., and Waterhouse, P.M. (2008). RNA silencing in plants: yesterday, today, and tomorrow.\u00a0Plant physiology,\u00a0147(2), 456\u2013468. https://doi.org/10.1104/pp.108.117275\r\n\r\n101. Lustig, A., and Levine, A.J. (1992). One hundred years of virology.\u00a0Journal of virology,\u00a066(8), 4629\u20134631. https://doi.org/10.1128/JVI.66.8.4629-4631.1992\r\n\r\n102. Taylor, M.W. (2014). Viruses and Man: A History of Interactions. Introduction: A Short History of Virology, 1-22. doi:\u00a010.1007/978-3-319-07758-1_1\r\n\r\n103. D\u00fcrst, M., Gissmann, L., Ikenberg, H., and zur Hausen, H. (1983). A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a080(12), 3812\u20133815. https://doi.org/10.1073/pnas.80.12.3812\r\n\r\n104. Poiesz, B.J., Ruscetti, F.W., Gazdar, A.F., Bunn, P.A., Minna, J.D., and Gallo, R.C. (1980). Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a077(12), 7415\u20137419. https://doi.org/10.1073/pnas.77.12.7415\r\n\r\n105. Barr\u00e9-Sinoussi, F., Chermann, J.C., Rey, F., Nugeyre, M.T., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., V\u00e9zinet-Brun, F., Rouzioux, C., Rozenbaum, W., and Montagnier, L. (1983). Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).\u00a0Science (New York, N.Y.),\u00a0220(4599), 868\u2013871. https://doi.org/10.1126/science.6189183\r\n\r\n106. Gallo, R.C., Salahuddin, S.Z., Popovic, M., Shearer, G.M., Kaplan, M., Haynes, B.F., Palker, T.J., Redfield, R., Oleske, J., and Safai, B. (1984). Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS.\u00a0Science (New York, N.Y.),\u00a0224(4648), 500\u2013503. https://doi.org/10.1126/science.6200936\r\n\r\n107. Levy, J.A., Hoffman, A.D., Kramer, S.M., Landis, J.A., Shimabukuro, J.M., and Oshiro, L.S. (1984). Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS.\u00a0Science (New York, N.Y.),\u00a0225(4664), 840\u2013842. https://doi.org/10.1126/science.6206563\r\n\r\n108. Choo, Q.L., Kuo, G., Weiner, A.J., Overby, L.R., Bradley, D.W., and Houghton, M. (1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.\u00a0Science (New York, N.Y.),\u00a0244(4902), 359\u2013362. https://doi.org/10.1126/science.2523562\r\n\r\n109. Andersen, K.G., Rambaut, A., Lipkin, W.I., Holmes, E.C., and Garry, R.F. (2020). The proximal origin of SARS-CoV-2.\u00a0Nature medicine,\u00a026(4), 450\u2013452. https://doi.org/10.1038/s41591-020-0820-9\r\n\r\n110. Zou, L., Ruan, F., Huang, M., Liang, L., Huang, H., Hong, Z., Yu, J., Kang, M., Song, Y., Xia, J., Guo, Q., Song, T., He, J., Yen, H.L., Peiris, M., and Wu, J. (2020). SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.\u00a0The New England journal of medicine,\u00a0382(12), 1177\u20131179. https://doi.org/10.1056/NEJMc2001737\r\n\r\n111. Nathues, H., Alarcon, P., Rushton, J., Jolie, R., Fiebig, K., Jimenez, M., Geurts, V., and Nathues, C. (2017). Cost of porcine reproductive and respiratory syndrome virus at individual farm level - An economic disease model.\u00a0Preventive veterinary medicine,\u00a0142, 16\u201329. https://doi.org/10.1016/j.prevetmed.2017.04.006\r\n\r\n112. Chi, J., VanLeeuwen, J. A., Weersink, A., & Keefe, G. P. (2002). Direct production losses and treatment costs from bovine viral diarrhoea virus, bovine leukosis virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum. Preventive veterinary medicine, 55(2), 137\u2013153. https://doi.org/10.1016/s0167-5877(02)00094-6\r\n\r\n113. Rubio, L., Galipienso, L., & Ferriol, I. (2020). Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution.\u00a0Frontiers in plant science,\u00a011, 1092. https://doi.org/10.3389/fpls.2020.01092\r\n\r\n\u2028114. Mumford, R.A., Macarthur, R., and Boonham, N. (2016). The role and challenges of new diagnostic technology in plant biosecurity.\u00a0Food Sec.\u00a08,\u00a0103\u2013109. https://doi.org/10.1007/s12571-015-0533-y\r\n\r\n115. Compans, R.W., & Roberts, P.C. (1994). Viruses as model systems in cell biology.\u00a0Methods in cell biology,\u00a043 Pt A, 3\u201342. https://doi.org/10.1016/s0091-679x(08)60596-8", "Chapter 2:\r\n\r\n1. Graham, R.L., and Baric, R.S. (2010). Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission.\u00a0Journal of virology,\u00a084(7), 3134\u20133146. https://doi.org/10.1128/JVI.01394-09\r\n\r\n2. Andersen, K.G., Rambaut, A., Lipkin, W.I., Holmes, E.C., and Garry, R. F. (2020). The proximal origin of SARS-CoV-2.\u00a0Nature medicine,\u00a026(4), 450\u2013452. https://doi.org/10.1038/s41591-020-0820-9\r\n\r\n3. Zou, L., Ruan, F., Huang, M., Liang, L., Huang, H., Hong, Z., Yu, J., Kang, M., Song, Y., Xia, J., Guo, Q., Song, T., He, J., Yen, H. L., Peiris, M., and Wu, J. (2020). SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.\u00a0The New England journal of medicine,\u00a0382(12), 1177\u20131179. https://doi.org/10.1056/NEJMc2001737\r\n\r\n4. Bar-On, Y. M., Flamholz, A., Phillips, R., and Milo, R. (2020). SARS-CoV-2 (COVID-19) by the numbers.\u00a0eLife,\u00a09, e57309. https://doi.org/10.7554/eLife.57309\r\n\r\n5. Wang, H., Li, X., Li, T., Zhang, S., Wang, L., Wu, X., and Liu, J. (2020). The genetic sequence, origin, and diagnosis of SARS-CoV-2.\u00a0European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology,\u00a039(9), 1629\u20131635. https://doi.org/10.1007/s10096-020-03899-4\r\n\r\n6. da Silva, S., Alves da Silva, C.T., Mendes, R., and Pena, L. (2020). Role of nonstructural proteins in the pathogenesis of SARS-CoV-2.\u00a0Journal of medical virology, 10.1002/jmv.25858. Advance online publication. https://doi.org/10.1002/jmv.25858\r\n\r\n7. Chen, L., and Zhong, L. (2020). Genomics functional analysis and drug screening of SARS-CoV-2.\u00a0Genes & diseases, 10.1016/j.gendis.2020.04.002. Advance online publication. https://doi.org/10.1016/j.gendis.2020.04.002\r\n\r\n8. Finkel, Y., Mizrahi, O., Nachshon, A., Weingarten-Gabbay, S., Morgenstern, D., Yahalom-Ronen, Y., Tamir, H., Achdout, H., Stein, D., Israeli, O., Beth-Din, A., Melamed, S., Weiss, S., Israely, T., Paran, N., Schwartz, M., and Stern-Ginossar, N. (2020). The coding capacity of SARS-CoV-2.\u00a0Nature, 10.1038/s41586-020-2739-1. Advance online publication. https://doi.org/10.1038/s41586-020-2739-1\r\n\r\n9. Maier, H.J., Neuman, B.W., Bickerton, E., Keep, S.M., Alrashedi, H., Hall, R., and Britton, P. (2016). Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity.\u00a0Scientific reports,\u00a06, 27126. https://doi.org/10.1038/srep27126\r\n\r\n10. Chow, K.T., Gale, M., Jr, and Loo, Y.M. (2018). RIG-I and Other RNA Sensors in Antiviral Immunity.\u00a0Annual review of immunology,\u00a036, 667\u2013694. https://doi.org/10.1146/annurev-immunol-042617-053309\r\n\r\n11 Jensen, S., and Thomsen, A.R. (2012). Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion.\u00a0Journal of virology,\u00a086(6), 2900\u20132910. https://doi.org/10.1128/JVI.05738-11\r\n\r\n12. Wilkins, C., and Gale, M., Jr (2010). Recognition of viruses by cytoplasmic sensors.\u00a0Current opinion in immunology,\u00a022(1), 41\u201347. https://doi.org/10.1016/j.coi.2009.12.003\r\n\r\n13. Stetson, D.B., and Medzhitov, R. (2006). Type I interferons in host defense.\u00a0Immunity,\u00a025(3), 373\u2013381. https://doi.org/10.1016/j.immuni.2006.08.007\r\n\r\n14. Beachboard, D.C., and Horner, S.M. (2016). Innate immune evasion strategies of DNA and RNA viruses.\u00a0Current opinion in microbiology,\u00a032, 113\u2013119. https://doi.org/10.1016/j.mib.2016.05.015\r\n\r\n15. Miller, D.M., Rahill, B.M., Boss, J.M., Lairmore, M.D., Durbin, J.E., Waldman, J.W., and Sedmak, D.D. (1998). Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway.\u00a0The Journal of experimental medicine,\u00a0187(5), 675\u2013683. https://doi.org/10.1084/jem.187.5.675\r\n\r\n16. Kempf, B.J., and Barton, D.J. (2008). Poliovirus 2A(Pro) increases viral mRNA and polysome stability coordinately in time with cleavage of eIF4G.\u00a0Journal of virology,\u00a082(12), 5847\u20135859. https://doi.org/10.1128/JVI.01514-07\r\n\r\n17. Lloyd, R.E. (2006). Translational control by viral proteinases.\u00a0Virus research,\u00a0119(1), 76\u201388. https://doi.org/10.1016/j.virusres.2005.10.016\r\n\r\n18. Kochs, G., Garc\u00eda-Sastre, A., and Mart\u00ednez-Sobrido, L. (2007). Multiple anti-interferon actions of the influenza A virus NS1 protein.\u00a0Journal of virology,\u00a081(13), 7011\u20137021. https://doi.org/10.1128/JVI.02581-06\r\n\r\n19. Zhang, L., Wang, J., Mu\u00f1oz-Moreno, R., Kim, M., Sakthivel, R., Mo, W., Shao, D., Anantharaman, A., Garc\u00eda-Sastre, A., Conrad, N.K., and Fontoura, B. (2018). Influenza Virus NS1 Protein-RNA Interactome Reveals Intron Targeting.\u00a0Journal of virology,\u00a092(24), e01634-18. https://doi.org/10.1128/JVI.01634-18\r\n\r\n20. Zhang, X., Tan, Y., Ling, Y., Lu, G., Liu, F., Yi, Z., Jia, X., Wu, M., Shi, B., Xu, S., Chen, J., Wang, W., Chen, B., Jiang, L., Yu, S., Lu, J., Wang, J., Xu, M., Yuan, Z., Zhang, Q., \u2026 Lu, H. (2020). Viral and host factors related to the clinical outcome of COVID-19.\u00a0Nature,\u00a0583(7816), 437\u2013440. https://doi.org/10.1038/s41586-020-2355-0\r\n\r\n21. Hadjadj, J., Yatim, N., Barnabei, L., Corneau, A., Boussier, J., Smith, N., P\u00e9r\u00e9, H., Charbit, B., Bondet, V., Chenevier-Gobeaux, C., Breillat, P., Carlier, N., Gauzit, R., Morbieu, C., P\u00e8ne, F., Marin, N., Roche, N., Szwebel, T.A., Merkling, S.H., Treluyer, J.M., \u2026 Terrier, B. (2020). Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients Science (New York, N.Y.),\u00a0369(6504), 718\u2013724. https://doi.org/10.1126/science.abc6027\r\n\r\n22. Lokugamage, K.G., Hage, A., de Vries, M., Valero-Jimenez, A.M., Schindewolf, C., Dittmann, M., Rajsbaum, R., and Menachery, V.D. (2020). Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV.\u00a0Journal of virology,\u00a094(23), e01410-20. https://doi.org/10.1128/JVI.01410-20\r\n\r\n23. Canton, J., Fehr, A.R., Fernandez-Delgado, R., Gutierrez-Alvarez, F.J., Sanchez-Aparicio, M.T., Garc\u00eda-Sastre, A., Perlman, S., Enjuanes, L., and Sola, I. (2018). MERS-CoV 4b protein interferes with the NF-\u03baB-dependent innate immune response during infection.\u00a0PLoS pathogens,\u00a014(1), e1006838. https://doi.org/10.1371/journal.ppat.1006838\r\n\r\n24. Kamitani, W., Huang, C., Narayanan, K., Lokugamage, K.G., and Makino, S. (2009). A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein.\u00a0Nature structural & molecular biology,\u00a016(11), 1134\u20131140. https://doi.org/10.1038/nsmb.1680\r\n\r\n\u202825. Lokugamage, K.G., Narayanan, K., Nakagawa, K., Terasaki, K., Ramirez, S.I., Tseng, C.T., and Makino, S. (2015). Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin.\u00a0Journal of virology,\u00a089(21), 10970\u201310981. https://doi.org/10.1128/JVI.01352-15\r\n\r\n26. Nakagawa, K., Narayanan, K., Wada, M., and Makino, S. (2018). Inhibition of Stress Granule Formation by Middle East Respiratory Syndrome Coronavirus 4a Accessory Protein Facilitates Viral Translation, Leading to Efficient Virus Replication.\u00a0Journal of virology,\u00a092(20), e00902-18. https://doi.org/10.1128/JVI.00902-18\r\n\r\n27. Sola, I., Mateos-Gomez, P.A., Almazan, F., Zu\u00f1iga, S., and Enjuanes, L. (2011). RNA-RNA and RNA-protein interactions in coronavirus replication and transcription.\u00a0RNA biology,\u00a08(2), 237\u2013248. https://doi.org/10.4161/rna.8.2.14991\r\n\r\n28. Peritz, T., Zeng, F., Kannanayakal, T.J., Kilk, K., Eir\u00edksd\u00f3ttir, E., Langel, U., Eberwine, J. (2006). Immunoprecipitation of mRNA-protein complexes.\u00a0Nature protocols,\u00a01(2), 577\u2013580. https://doi.org/10.1038/nprot.2006.82\r\n\r\n29. Keene, J.D., Komisarow, J.M., and Friedersdorf, M.B. (2006). RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts.\u00a0Nature protocols,\u00a01(1), 302\u2013307. https://doi.org/10.1038/nprot.2006.47\r\n\r\n30. Hendrickson, G.D., Kelley, D.R., Tenen, D., Bernstein, B., and Rinn, J.L. (2016). Widespread RNA binding by chromatin-associated proteins.\u00a0Genome biology,\u00a017, 28. https://doi.org/10.1186/s13059-016-0878-3\r\n\r\n31. Mili, S., and Steitz, J.A. (2004). Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses.\u00a0RNA (New York, N.Y.),\u00a010(11), 1692\u20131694. https://doi.org/10.1261/rna.7151404\r\n\r\n32. Darnell, R.B. (2010). HITS-CLIP: panoramic views of protein-RNA regulation in living cells.\u00a0Wiley interdisciplinary reviews. RNA,\u00a01(2), 266\u2013286. https://doi.org/10.1002/wrna.31\r\n\r\n33. K\u00f6nig, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D.J., Luscombe, N.M., and Ule, J. (2010). iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution.\u00a0Nature structural & molecular biology,\u00a017(7), 909\u2013915. https://doi.org/10.1038/nsmb.1838\r\n\r\n34. Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., Rothballer, A., Ascano, M., Jr, Jungkamp, A.C., Munschauer, M., Ulrich, A., Wardle, G.S., Dewell, S., Zavolan, M., and Tuschl, T. (2010). Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.\u00a0Cell,\u00a0141(1), 129\u2013141. https://doi.org/10.1016/j.cell.2010.03.009\r\n\r\n35. Zhao, J., Sun, B.K., Erwin, J.A., Song, J.J., and Lee, J.T. (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.\u00a0Science (New York, N.Y.),\u00a0322(5902), 750\u2013756. https://doi.org/10.1126/science.1163045\r\n\r\n36. Cifuentes-Rojas, C., Hernandez, A.J., Sarma, K., and Lee, J.T. (2014). Regulatory interactions between RNA and polycomb repressive complex 2.\u00a0Molecular cell,\u00a055(2), 171\u2013185. https://doi.org/10.1016/j.molcel.2014.05.009\r\n\r\n37. Schoeftner, S., Sengupta, A.K., Kubicek, S., Mechtler, K., Spahn, L., Koseki, H., Jenuwein, T., and Wutz, A. (2006). Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing.\u00a0The EMBO journal,\u00a025(13), 3110\u20133122. https://doi.org/10.1038/sj.emboj.7601187\r\n\r\n38. Kalantry, S., and Magnuson, T. (2006). The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation.\u00a0PLoS genetics,\u00a02(5), e66. https://doi.org/10.1371/journal.pgen.0020066\r\n\r\n39. Plath, K., Fang, J., Mlynarczyk-Evans, S.K., Cao, R., Worringer, K.A., Wang, H., de la Cruz, C.C., Otte, A.P., Panning, B., and Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation.\u00a0Science (New York, N.Y.),\u00a0300(5616), 131\u2013135. https://doi.org/10.1126/science.1084274\r\n\r\n40. da Rocha, S.T., Boeva, V., Escamilla-Del-Arenal, M., Ancelin, K., Granier, C., Matias, N. R., Sanulli, S., Chow, J., Schulz, E., Picard, C., Kaneko, S., Helin, K., Reinberg, D., Stewart, A. F., Wutz, A., Margueron, R., and Heard, E. (2014). Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.\u00a0Molecular cell,\u00a053(2), 301\u2013316. https://doi.org/10.1016/j.molcel.2014.01.002\r\n\r\n41. McHugh, C.A., Chen, C.K., Chow, A., Surka, C.F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M.J., Shishkin, A.A., Su, J., Lander, E.S., Hess, S., Plath, K., and Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.\u00a0Nature,\u00a0521(7551), 232\u2013236. https://doi.org/10.1038/nature14443\r\n\r\n42. Kohlmaier, A., Savarese, F., Lachner, M., Martens, J., Jenuwein, T., and Wutz, A. (2004). A chromosomal memory triggered by Xist regulates histone methylation in X inactivation.\u00a0PLoS biology,\u00a02(7), E171. https://doi.org/10.1371/journal.pbio.0020171\r\n\r\n43. Portoso, M., Ragazzini, R., Bren\u010di\u010d, \u017d., Moiani, A., Michaud, A., Vassilev, I., Wassef, M., Servant, N., Sargueil, B., and Margueron, R. (2017). PRC2 is dispensable for\u00a0HOTAIR-mediated transcriptional repression.\u00a0The EMBO journal,\u00a036(8), 981\u2013994. https://doi.org/10.15252/embj.201695335\r\n\r\n44. Brockdorff, N. (2013). Noncoding RNA and Polycomb recruitment.\u00a0RNA (New York, N.Y.),\u00a019(4), 429\u2013442. https://doi.org/10.1261/rna.037598.112\r\n\r\n45. Davidovich, C., Zheng, L., Goodrich, K.J., and Cech, T.R. (2013). Promiscuous RNA binding by Polycomb repressive complex 2.\u00a0Nature structural & molecular biology,\u00a020(11), 1250\u20131257. https://doi.org/10.1038/nsmb.2679\r\n\r\n46. Wang, X., Goodrich, K.J., Gooding, A.R., Naeem, H., Archer, S., Paucek, R.D., Youmans, D.T., Cech, T.R., and Davidovich, C. (2017). Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines.\u00a0Molecular cell,\u00a065(6), 1056\u20131067.e5. https://doi.org/10.1016/j.molcel.2017.02.003\r\n\r\n47. Beltran, M., Yates, C.M., Skalska, L., Dawson, M., Reis, F.P., Viiri, K., Fisher, C.L., Sibley, C.R., Foster, B.M., Bartke, T., Ule, J., and Jenner, R.G. (2016). The interaction of PRC2 with RNA or chromatin is mutually antagonistic.\u00a0Genome research,\u00a026(7), 896\u2013907. https://doi.org/10.1101/gr.197632.115\r\n\r\n48. Kaneko, S., Bonasio, R., Salda\u00f1a-Meyer, R., Yoshida, T., Son, J., Nishino, K., Umezawa, A., and Reinberg, D. (2014). Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin.\u00a0Molecular cell,\u00a053(2), 290\u2013300. https://doi.org/10.1016/j.molcel.2013.11.012\r\n\r\n49. Khalil, A.M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B.E., van Oudenaarden, A., Regev, A., Lander, E.S., and Rinn, J.L. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0106(28), 11667\u201311672. https://doi.org/10.1073/pnas.0904715106\r\n\r\n50. Zhao, J., Ohsumi, T.K., Kung, J.T., Ogawa, Y., Grau, D.J., Sarma, K., Song, J.J., Kingston, R.E., Borowsky, M., and Lee, J.T. (2010). Genome-wide identification of polycomb-associated RNAs by RIP-seq.\u00a0Molecular cell,\u00a040(6), 939\u2013953. https://doi.org/10.1016/j.molcel.2010.12.011\r\n\r\n51. Kaneko, S., Son, J., Shen, S.S., Reinberg, D., and Bonasio, R. (2013). PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.\u00a0Nature structural & molecular biology,\u00a020(11), 1258\u20131264. https://doi.org/10.1038/nsmb.2700\r\n\r\n52. Pandey, R.R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini-Dinardo, D., and Kanduri, C. (2008). Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation.\u00a0Molecular cell,\u00a032(2), 232\u2013246. https://doi.org/10.1016/j.molcel.2008.08.022\r\n\r\n53. Los, G.V., Encell, L.P., McDougall, M.G., Hartzell, D.D., Karassina, N., Zimprich, C., Wood, M.G., Learish, R., Ohana, R.F., Urh, M., Simpson, D., Mendez, J., Zimmerman, K., Otto, P., Vidugiris, G., Zhu, J., Darzins, A., Klaubert, D.H., Bulleit, R.F., and Wood, K.V. (2008). HaloTag: a novel protein labeling technology for cell imaging and protein analysis.\u00a0ACS chemical biology,\u00a03(6), 373\u2013382. https://doi.org/10.1021/cb800025k\r\n\r\n54. Zakeri, B., Fierer, J. O., Celik, E., Chittock, E.C., Schwarz-Linek, U., Moy, V.T., and Howarth, M. (2012). Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0109(12), E690\u2013E697. https://doi.org/10.1073/pnas.1115485109\r\n\r\n55. Ray, D., Kazan, H., Chan, E.T., Pe\u00f1a Castillo, L., Chaudhry, S., Talukder, S., Blencowe, B.J., Morris, Q., and Hughes, T.R. (2009). Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins.\u00a0Nature biotechnology,\u00a027(7), 667\u2013670. https://doi.org/10.1038/nbt.1550\r\n\r\n56. Sokolowski, M., and Schwartz, S. (2001). Heterogeneous nuclear ribonucleoprotein C binds exclusively to the functionally important UUUUU-motifs in the human papillomavirus type-1 AU-rich inhibitory element.\u00a0Virus research,\u00a073(2), 163\u2013175. https://doi.org/10.1016/s0168-1702(00)00238-0\r\n\r\n57. Uren, P.J., Bahrami-Samani, E., de Araujo, P.R., Vogel, C., Qiao, M., Burns, S.C., Smith, A. D., and Penalva, L.O. (2016). High-throughput analyses of hnRNP H1 dissects its multi-functional aspect.\u00a0RNA biology,\u00a013(4), 400\u2013411. https://doi.org/10.1080/15476286.2015.1138030\r\n\r\n58. Xiao, R., Tang, P., Yang, B., Huang, J., Zhou, Y., Shao, C., Li, H., Sun, H., Zhang, Y., and Fu, X.D. (2012). Nuclear matrix factor hnRNP U/SAF-A exerts a global control of alternative splicing by regulating U2 snRNP maturation.\u00a0Molecular cell,\u00a045(5), 656\u2013668. https://doi.org/10.1016/j.molcel.2012.01.009\r\n\r\n59. Simard, M.J., and Chabot, B. (2002). SRp30c is a repressor of 3' splice site utilization. Molecular and cellular biology,\u00a022(12), 4001\u20134010. https://doi.org/10.1128/mcb.22.12.4001-4010.2002\r\n\r\n60. Siomi, H., Choi, M., Siomi, M.C., Nussbaum, R.L., and Dreyfuss, G. (1994). Essential role for KH domains in RNA binding: impaired RNA binding by a mutation in the KH domain of FMR1 that causes fragile X syndrome.\u00a0Cell,\u00a077(1), 33\u201339. https://doi.org/10.1016/0092-8674(94)90232-1\r\n\r\n61. Yisraeli, J.K. (2005). VICKZ proteins: a multi-talented family of regulatory RNA-binding proteins.\u00a0Biology of the cell,\u00a097(1), 87\u201396. https://doi.org/10.1042/BC20040151\r\n\r\n62. Baron-Benhamou, J., Gehring, N.H., Kulozik, A.E., and Hentze, M.W. (2004). Using the lambdaN peptide to tether proteins to RNAs.\u00a0Methods in molecular biology (Clifton, N.J.),\u00a0257, 135\u2013154. https://doi.org/10.1385/1-59259-750-5:135\r\n\r\n65. S\u00e9raphin, B., Kretzner, L., and Rosbash, M. (1988). A U1 snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5' cleavage site.\u00a0The EMBO journal,\u00a07(8), 2533\u20132538.\r\n\r\n66. Majumdar, D., Frankiw, L., Burns, C., Garcia-Flores, Y., and Baltimore, D. (2018). Programmed Delayed Splicing: A Mechanism for Timed Inflammatory Gene Expression. BioRxiv 443796.\r\n\r\n67. Decroly, E., Debarnot, C., Ferron, F., Bouvet, M., Coutard, B., Imbert, I., Gluais, L., Papageorgiou, N., Sharff, A., Bricogne, G., Ortiz-Lombardia, M., Lescar, J., and Canard, B. (2011). Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex.\u00a0PLoS pathogens,\u00a07(5), e1002059. https://doi.org/10.1371/journal.ppat.1002059\r\n\r\n68. Kurosaki, T., Popp, M.W., and Maquat, L.E. (2019). Quality and quantity control of gene expression by nonsense-mediated mRNA decay.\u00a0Nature reviews. Molecular cell biology,\u00a020(7), 406\u2013420. https://doi.org/10.1038/s41580-019-0126-2\r\n\r\n69. Brockway, S.M., and Denison, M.R. (2005). Mutagenesis of the murine hepatitis virus nsp1-coding region identifies residues important for protein processing, viral RNA synthesis, and viral replication.\u00a0Virology,\u00a0340(2), 209\u2013223. https://doi.org/10.1016/j.virol.2005.06.035\r\n\r\n70. Narayanan, K., Ramirez, S.I., Lokugamage, K.G., and Makino, S. (2015). Coronavirus nonstructural protein 1: Common and distinct functions in the regulation of host and viral gene expression.\u00a0Virus research,\u00a0202, 89\u2013100. https://doi.org/10.1016/j.virusres.2014.11.019\r\n\r\n71. Tanaka, T., Kamitani, W., DeDiego, M.L., Enjuanes, L., and Matsuura, Y. (2012). Severe acute respiratory syndrome coronavirus nsp1 facilitates efficient propagation in cells through a specific translational shutoff of host mRNA.\u00a0Journal of virology,\u00a086(20), 11128\u201311137. https://doi.org/10.1128/JVI.01700-12\r\n\r\n72. Simonetti, A., Guca, E., Bochler, A., Kuhn, L., and Hashem, Y. (2020). Structural Insights into the Mammalian Late-Stage Initiation Complexes.\u00a0Cell reports,\u00a031(1), 107497. https://doi.org/10.1016/j.celrep.2020.03.061\r\n\r\n73. Ogle, J.M., Brodersen, D.E., Clemons, W.M., Jr, Tarry, M.J., Carter, A.P., and Ramakrishnan, V. (2001). Recognition of cognate transfer RNA by the 30S ribosomal subunit.\u00a0Science (New York, N.Y.),\u00a0292(5518), 897\u2013902. https://doi.org/10.1126/science.1060612\r\n\r\n74. Brown, A., Baird, M.R., Yip, M.C., Murray, J., and Shao, S. (2018). Structures of translationally inactive mammalian ribosomes.\u00a0eLife,\u00a07, e40486. https://doi.org/10.7554/eLife.40486\r\n\r\n75. Ben-Shem, A., Garreau de Loubresse, N., Melnikov, S., Jenner, L., Yusupova, G., and Yusupov, M. (2011). The structure of the eukaryotic ribosome at 3.0 \u00c5 resolution.\u00a0Science (New York, N.Y.),\u00a0334(6062), 1524\u20131529. https://doi.org/10.1126/science.1212642\r\n\r\n76. Thoms, M., Buschauer, R., Ameismeier, M., Koepke, L., Denk, T., Hirschenberger, M., Kratzat, H., Hayn, M., Mackens-Kiani, T., Cheng, J., Straub, J.H., St\u00fcrzel, C.M., Fr\u00f6hlich, T., Berninghausen, O., Becker, T., Kirchhoff, F., Sparrer, K., and Beckmann, R. (2020). Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2.\u00a0Science (New York, N.Y.),\u00a0369(6508), 1249\u20131255. https://doi.org/10.1126/science.abc8665\r\n\r\n77. Schmidt, E.K., Clavarino, G., Ceppi, M., and Pierre, P. (2009). SUnSET, a nonradioactive method to monitor protein synthesis.\u00a0Nature methods,\u00a06(4), 275\u2013277. https://doi.org/10.1038/nmeth.1314\r\n\r\n78. Narayanan, K., Huang, C., Lokugamage, K., Kamitani, W., Ikegami, T., Tseng, C.T., and Makino, S. (2008). Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells.\u00a0Journal of virology,\u00a082(9), 4471\u20134479. https://doi.org/10.1128/JVI.02472-07\r\n\r\n79. Alexopoulou, L., Holt, A.C., Medzhitov, R., and Flavell, R.A. (2001). Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.\u00a0Nature,\u00a0413(6857), 732\u2013738. https://doi.org/10.1038/35099560\r\n\r\n80. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K.J., Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C.S., Reis e Sousa, C., Matsuura, Y., Fujita, T., and Akira, S. (2006). Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses.\u00a0Nature,\u00a0441(7089), 101\u2013105. https://doi.org/10.1038/nature04734\r\n\r\n81. Gaglia, M.M., Covarrubias, S., Wong, W., and Glaunsinger, B.A. (2012). A common strategy for host RNA degradation by divergent viruses.\u00a0Journal of virology,\u00a086(17), 9527\u20139530. https://doi.org/10.1128/JVI.01230-12\r\n\r\n82. Kim, D., Lee, J.Y., Yang, J.S., Kim, J.W., Kim, V.N., and Chang, H. (2020). The Architecture of SARS-CoV-2 Transcriptome.\u00a0Cell,\u00a0181(4), 914\u2013921.e10. https://doi.org/10.1016/j.cell.2020.04.011\r\n\r\n83. Akopian, D., Shen, K., Zhang, X., and Shan, S.O. (2013). Signal recognition particle: an essential protein-targeting machine.\u00a0Annual review of biochemistry,\u00a082, 693\u2013721. https://doi.org/10.1146/annurev-biochem-072711-164732\r\n\r\n84. Holtkamp, W., Lee, S., Bornemann, T., Senyushkina, T., Rodnina, M.V., and Wintermeyer, W. (2012). Dynamic switch of the signal recognition particle from scanning to targeting.\u00a0Nature structural & molecular biology,\u00a019(12), 1332\u20131337. https://doi.org/10.1038/nsmb.2421\r\n\r\n85. Parker, M.S., Balasubramaniam, A., Sallee, F.R., and Parker, S.L. (2018). The Expansion Segments of 28S Ribosomal RNA Extensively Match Human Messenger RNAs.\u00a0Frontiers in genetics,\u00a09, 66. https://doi.org/10.3389/fgene.2018.00066\r\n\r\n86. Zhang, Y., Ma, C., Yuan, Y., Zhu, J., Li, N., Chen, C., Wu, S., Yu, L., Lei, J., and Gao, N. (2014). Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome.\u00a0Nature structural & molecular biology,\u00a021(12), 1042\u20131046. https://doi.org/10.1038/nsmb.2908\r\n\r\n87. Wild, K., Aleksi\u0107, M., Lapouge, K., Juaire, K.D., Flemming, D., Pfeffer, S., and Sinning, I. (2020). MetAP-like Ebp1 occupies the human ribosomal tunnel exit and recruits flexible rRNA expansion segments.\u00a0Nature communications,\u00a011(1), 776. https://doi.org/10.1038/s41467-020-14603-7\r\n\r\n88. Izon, D.J., Punt, J.A., Xu, L., Karnell, F.G., Allman, D., Myung, P.S., Boerth, N.J., Pui, J.C., Koretzky, G.A., and Pear, W.S. (2001). Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength.\u00a0Immunity,\u00a014(3), 253\u2013264. https://doi.org/10.1016/s1074-7613(01)00107-8\r\n\r\n89. Sutton, G., Fry, E., Carter, L., Sainsbury, S., Walter, T., Nettleship, J., Berrow, N., Owens, R., Gilbert, R., Davidson, A., Siddell, S., Poon, L.L., Diprose, J., Alderton, D., Walsh, M., Grimes, J.M., and Stuart, D.I. (2004). The nsp9 replicase protein of SARS-coronavirus, structure and functional insights.\u00a0Structure (London, England : 1993),\u00a012(2), 341\u2013353. https://doi.org/10.1016/j.str.2004.01.016\r\n\r\n90. Vermeire, K., Bell, T.W., Van Puyenbroeck, V., Giraut, A., Noppen, S., Liekens, S., Schols, D., Hartmann, E., Kalies, K.U., and Marsh, M. (2014). Signal peptide-binding drug as a selective inhibitor of co-translational protein translocation.\u00a0PLoS biology,\u00a012(12), e1002011. https://doi.org/10.1371/journal.pbio.1002011\r\n\r\n91. Zhou, Q., Chen, V., Shannon, C.P., Wei, X.S., Xiang, X., Wang, X., Wang, Z.H., Tebbutt, S. J., Kollmann, T.R., and Fish, E.N. (2020). Interferon-\u03b12b Treatment for COVID-19.\u00a0Frontiers in immunology,\u00a011, 1061. https://doi.org/10.3389/fimmu.2020.01061\r\n\r\n92. Liaud, N., Horlbeck, M.A., Gilbert, L.A., Gjoni, K., Weissman, J.S., and Cate, J. (2019). Cellular response to small molecules that selectively stall protein synthesis by the ribosome PLoS genetics,\u00a015(3), e1008057. https://doi.org/10.1371/journal.pgen.1008057\r\n\r\n93. Hermann, T. (2016). Small molecules targeting viral RNA.\u00a0Wiley interdisciplinary reviews. RNA,\u00a07(6), 726\u2013743. https://doi.org/10.1002/wrna.1373\r\n\r\n94. Hansen, T.H., and Bouvier, M. (2009). MHC class I antigen presentation: learning from viral evasion strategies.\u00a0Nature reviews. Immunology,\u00a09(7), 503\u2013513. https://doi.org/10.1038/nri2575\u2028\r\n\r\n95. Weston, C.R., and Davis, R.J. (2007). The JNK signal transduction pathway.\u00a0Current opinion in cell biology,\u00a019(2), 142\u2013149. https://doi.org/10.1016/j.ceb.2007.02.001\r\n\r\n96. Cope, G.A., and Deshaies, R.J. (2003). COP9 signalosome: a multifunctional regulator of SCF and other cullin-based ubiquitin ligases.\u00a0Cell,\u00a0114(6), 663\u2013671. https://doi.org/10.1016/s0092-8674(03)00722-0\r\n\r\n97. Claret, F.X., Hibi, M., Dhut, S., Toda, T., and Karin, M. (1996). A new group of conserved coactivators that increase the specificity of AP-1 transcription factors.\u00a0Nature,\u00a0383(6599), 453\u2013457. https://doi.org/10.1038/383453a0\r\n\r\n98. Lungu, G.F., Stoica, G., and Wong, P.K. (2008). Down-regulation of Jab1, HIF-1alpha, and VEGF by Moloney murine leukemia virus-ts1 infection: a possible cause of neurodegeneration. \u2028Journal of neurovirology,\u00a014(3), 239\u2013251. https://doi.org/10.1080/13550280802093919\r\n\r\n99. Oh, W., Yang, M.R., Lee, E.W., Park, K.M., Pyo, S., Yang, J.S., Lee, H.W., and Song, J. (2006). Jab1 mediates cytoplasmic localization and degradation of West Nile virus capsid protein.\u00a0The Journal of biological chemistry,\u00a0281(40), 30166\u201330174. https://doi.org/10.1074/jbc.M602651200\r\n\r\n100. Tanaka, Y., Kanai, F., Ichimura, T., Tateishi, K., Asaoka, Y., Guleng, B., Jazag, A., Ohta, M., Imamura, J., Ikenoue, T., Ijichi, H., Kawabe, T., Isobe, T., and Omata, M. (2006). The hepatitis B virus X protein enhances AP-1 activation through interaction with Jab1.\u00a0Oncogene,\u00a025(4), 633\u2013642. https://doi.org/10.1038/sj.onc.1209093\r\n\r\n101. Kim, D.K., Knapp, J.J., Kuang, D., Chawla, A., Cassonnet, P., Lee, H., Sheykhkarimli, D., Samavarchi-Tehrani, P., Abdouni, H., Rayhan, A., Li, R., Pogoutse, O., Coyaud, \u00c9., van der Werf, S., Demeret, C., Gingras, A.C., Taipale, M., Raught, B., Jacob, Y., and Roth, F.P. (2020). A Comprehensive, Flexible Collection of SARS-CoV-2 Coding Regions.\u00a0G3 (Bethesda, Md.),\u00a010(9), 3399\u20133402. https://doi.org/10.1534/g3.120.401554\r\n\r\n102. Van Nostrand, E.L., Pratt, G.A., Shishkin, A.A., Gelboin-Burkhart, C., Fang, M.Y., Sundararaman, B., Blue, S.M., Nguyen, T.B., Surka, C., Elkins, K., Stanton, R., Rigo, F., Guttman, M., and Yeo, G.W. (2016). Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).\u00a0Nature methods,\u00a013(6), 508\u2013514. https://doi.org/10.1038/nmeth.3810\r\n\r\n103. Guttman, M., Amit, I., Garber, M., French, C., Lin, M.F., Feldser, D., Huarte, M., Zuk, O., Carey, B.W., Cassady, J.P., Cabili, M.N., Jaenisch, R., Mikkelsen, T.S., Jacks, T., Hacohen, N., Bernstein, B.E., Kellis, M., Regev, A., Rinn, J.L., and Lander, E.S. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458 (7235), 223-227. https://doi.org/10.1038/nature07672\r\n\r\n104. Guttman, M., Garber, M., Levin, J.Z., Donaghey, J., Robinson, J., Adiconis, X., Fan, L., Koziol, M.J., Gnirke, A., Nusbaum, C., Rinn, J.L., Lander, E.S., and Regev, A. (2010). Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs.\u00a0Nature biotechnology,\u00a028(5), 503\u2013510. https://doi.org/10.1038/nbt.1633\r\n\r\n105. Naus, J.I. (1982). Approximations for Distributions of Scan Statistics. J. Am. Stat. Assoc. 77 (177).\r\n\r\n106. Robinson, J.T., Thorvaldsd\u00f3ttir, H., Winckler, W., Guttman, M., Lander, E.S., Getz, G., and Mesirov, J.P. (2011). Integrative genomics viewer.\u00a0Nature biotechnology,\u00a029(1), 24\u201326. https://doi.org/10.1038/nbt.1754\r\n\r\n107. Liberzon, A., Birger, C., Thorvaldsd\u00f3ttir, H., Ghandi, M., Mesirov, J.P., and Tamayo, P. (2015). The Molecular Signatures Database (MSigDB) hallmark gene set collection.\u00a0Cell systems,\u00a01(6), 417\u2013425. https://doi.org/10.1016/j.cels.2015.12.004\r\n\r\n108. Yang, J., Anishchenko, I., Park, H., Peng, Z., Ovchinnikov, S., and Baker, D. (2020). Improved protein structure prediction using predicted interresidue orientations.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0117(3), 1496\u20131503. https://doi.org/10.1073/pnas.1914677117\r\n\r\n109. Webb, B., and Sali, A. (2016). Comparative Protein Structure Modeling Using MODELLER.\u00a0Current protocols in bioinformatics,\u00a054, 5.6.1\u20135.6.37. https://doi.org/10.1002/cpbi.3\r\n\r\n110. Delano, W. (2002). PyMOL molecular graphics system.\r\n\r\n111. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., and Bourne, P.E. (2000). The Protein Data Bank.\u00a0Nucleic acids research,\u00a028(1), 235\u2013242. https://doi.org/10.1093/nar/28.1.235\r\n\r\n112. Kim, S.I., Oceguera-Yanez, F., Sakurai, C., Nakagawa, M., Yamanaka, S., and Woltjen, K. (2016). Inducible Transgene Expression in Human iPS Cells Using Versatile All-in-One piggyBac Transposons.\u00a0Methods in molecular biology (Clifton, N.J.),\u00a01357, 111\u2013131. https://doi.org/10.1007/7651_2015_251\r\n\r\n113. Alberti, S., Saha, S., Woodruff, J.B., Franzmann, T.M., Wang, J., and Hyman, A.A. (2018). A User's Guide for Phase Separation Assays with Purified Proteins.\u00a0Journal of molecular biology,\u00a0430(23), 4806\u20134820. https://doi.org/10.1016/j.jmb.2018.06.038\r\n\r\n114. Jao, C.Y., and Salic, A. (2008). Exploring RNA transcription and turnover in vivo by using click chemistry.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0105(41), 15779\u201315784. https://doi.org/10.1073/pnas.0808480105\r\n\r\n115. Hong, V., Presolski, S.I., Ma, C., and Finn, M.G. (2009). Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation.\u00a0Angewandte Chemie (International ed. in English),\u00a048(52), 9879\u20139883. https://doi.org/10.1002/anie.200905087\r\n\r\n116. Rodriguez, J.M., Maietta, P., Ezkurdia, I., Pietrelli, A., Wesselink, J.J., Lopez, G., Valencia, A., and Tress, M.L. (2013). APPRIS: annotation of principal and alternative splice isoforms.\u00a0Nucleic acids research,\u00a041(Database issue), D110\u2013D117. https://doi.org/10.1093/nar/gks1058\r\n\r\n117. Banerjee, A.K., Blanco, M.R., Bruce, E.A., Honson, D.D., Chen, L.M., Chow, A., Bhat, P., Ollikainen, N., Quinodoz, S.A., Loney, C., Thai, J., Miller, Z.D., Lin, A.E., Schmidt, M.M., Stewart, D.G., Goldfarb, D., De Lorenzo, G., Rihn, S.J., Voorhees, R.M., Botten, J.W., \u2026 Guttman, M. (2020). SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.\u00a0Cell, S0092-8674(20)31310-6. Advance online publication. https://doi.org/10.1016/j.cell.2020.10.004\r\n\r\n118. Mayr, C., and Bartel, D.P. (2009). Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells.\u00a0Cell,\u00a0138(4), 673\u2013684. https://doi.org/10.1016/j.cell.2009.06.016\r\n\r\n119. Chen, C.K., Blanco, M., Jackson, C., Aznauryan, E., Ollikainen, N., Surka, C., Chow, A., Cerase, A., McDonel, P., and Guttman, M. (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing.\u00a0Science (New York, N.Y.),\u00a0354(6311), 468\u2013472. https://doi.org/10.1126/science.aae0047\r\n\r\n120. Cirillo, D., Blanco, M., Armaos, A., Buness, A., Avner, P., Guttman, M., Cerase, A., and Tartaglia, G.G. (2016). Quantitative predictions of protein interactions with long noncoding RNAs.\u00a0Nature methods,\u00a014(1), 5\u20136. https://doi.org/10.1038/nmeth.4100\r\n\r\n121. Shishkin, A.A., Giannoukos, G., Kucukural, A., Ciulla, D., Busby, M., Surka, C., Chen, J., Bhattacharyya, R.P., Rudy, R.F., Patel, M.M., Novod, N., Hung, D.T., Gnirke, A., Garber, M., Guttman, M., and Livny, J. (2015). Simultaneous generation of many RNA-seq libraries in a single reaction.\u00a0Nature methods,\u00a012(4), 323\u2013325. https://doi.org/10.1038/nmeth.3313\r\n\r\n122. Bolger, A.M., Lohse, M., and Usadel, B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data.\u00a0Bioinformatics (Oxford, England),\u00a030(15), 2114\u20132120. https://doi.org/10.1093/bioinformatics/btu170\r\n\r\n123. Xu, H., Luo, X., Qian, J., Pang, X., Song, J., Qian, G., Chen, J., and Chen, S. (2012). FastUniq: a fast de novo duplicates removal tool for paired short reads.\u00a0PloS one,\u00a07(12), e52249. https://doi.org/10.1371/journal.pone.0052249\r\n\r\n124. Lassmann, T., Hayashizaki, Y., and Daub, C.O. (2009). TagDust--a program to eliminate artifacts from next generation sequencing data.\u00a0Bioinformatics (Oxford, England),\u00a025(21), 2839\u20132840. https://doi.org/10.1093/bioinformatics/btp527\r\n\r\n125. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., and Gingeras, T.R. (2013). STAR: ultrafast universal RNA-seq aligner.\u00a0Bioinformatics (Oxford, England),\u00a029(1), 15\u201321. https://doi.org/10.1093/bioinformatics/bts635\r\n\r\n126. Charenton, C., Wilkinson, M.E., and Nagai, K. (2019). Mechanism of 5' splice site transfer for human spliceosome activation.\u00a0Science (New York, N.Y.),\u00a0364(6438), 362\u2013367. https://doi.org/10.1126/science.aax3289\r\n\r\n127. Ameismeier, M., Cheng, J., Berninghausen, O., and Beckmann, R. (2018). Visualizing late states of human 40S ribosomal subunit maturation.\u00a0Nature,\u00a0558(7709), 249\u2013253. https://doi.org/10.1038/s41586-018-0193-0\r\n\r\n128. Kuglstatter, A., Oubridge, C., and Nagai, K. (2002). Induced structural changes of 7SL RNA during the assembly of human signal recognition particle.\u00a0Nature structural biology,\u00a09(10), 740\u2013744. https://doi.org/10.1038/nsb843\r\n\r\n129. Voorhees, R.M., and Hegde, R.S. (2015). Structures of the scanning and engaged states of the mammalian SRP-ribosome complex.\u00a0eLife,\u00a04, e07975. https://doi.org/10.7554/eLife.07975", "Chapter 3: \r\n\r\n1. S\u00e9raphin, B., Kretzner, L., and Rosbash, M. (1988). A U1 snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5\u2019 cleavage site.\u00a0The EMBO journal,\u00a07(8), 2533\u20132538.\r\n\r\n2. Quinodoz, S., and Guttman, M. (2014). Long noncoding RNAs: an emerging link between gene regulation and nuclear organization.\u00a0Trends in cell biology,\u00a024(11), 651\u2013663. https://doi.org/10.1016/j.tcb.2014.08.009\r\n\r\n3. McHugh, C.A., Chen, C.K., Chow, A., Surka, C.F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M.J., Shishkin, A.A., Su, J., Lander, E.S., Hess, S., Plath, K., and Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.\u00a0Nature,\u00a0521(7551), 232\u2013236. https://doi.org/10.1038/nature14443\r\n\r\n4. Chu, C., Zhang, Q.C., da Rocha, S.T., Flynn, R.A., Bharadwaj, M., Calabrese, J.M., Magnuson, T., Heard, E., and Chang, H.Y. (2015). Systematic discovery of Xist RNA binding proteins.\u00a0Cell,\u00a0161(2), 404\u2013416. https://doi.org/10.1016/j.cell.2015.03.025\r\n\r\n5. Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T.B., and Brockdorff, N. (2015). A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.\u00a0Cell reports,\u00a012(4), 562\u2013572. https://doi.org/10.1016/j.celrep.2015.06.053\r\n\r\n6. Monfort, A., Di Minin, G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., and Wutz, A. (2015). Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.\u00a0Cell reports,\u00a012(4), 554\u2013561. https://doi.org/10.1016/j.celrep.2015.06.067\r\n\r\n7. Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E., and Cech, T.R. (1982). Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena.\u00a0Cell,\u00a031(1), 147\u2013157. https://doi.org/10.1016/0092-8674(82)90414-7\r\n\r\n8. Steitz, T.A., and Steitz, J.A. (1993). A general two-metal-ion mechanism for catalytic RNA.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a090(14), 6498\u20136502. https://doi.org/10.1073/pnas.90.14.6498\r\n\r\n8. Cech, T.R., and Steitz, J.A. (2014). The noncoding RNA revolution-trashing old rules to forge new ones.\u00a0Cell,\u00a0157(1), 77\u201394. https://doi.org/10.1016/j.cell.2014.03.008\r\n\r\n9. Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., Hayward, D.C., Ball, E.E., Degnan, B., M\u00fcller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E., and Ruvkun, G. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.\u00a0Nature,\u00a0408(6808), 86\u201389. https://doi.org/10.1038/35040556\r\n\r\n10. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., & Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs.\u00a0Science (New York, N.Y.),\u00a0294(5543), 853\u2013858. https://doi.org/10.1126/science.1064921\r\n\r\n11. Lau, N.C., Lim, L.P., Weinstein, E.G., and Bartel, D.P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.\u00a0Science (New York, N.Y.),\u00a0294(5543), 858\u2013862. https://doi.org/10.1126/science.1065062\r\n\r\n12. Lee, R.C., and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans.\u00a0Science (New York, N.Y.),\u00a0294(5543), 862\u2013864. https://doi.org/10.1126/science.1065329\r\n\r\n13. Gurtan, A.M., and Sharp, P.A. (2013). The role of miRNAs in regulating gene expression networks.\u00a0Journal of molecular biology,\u00a0425(19), 3582\u20133600. https://doi.org/10.1016/j.jmb.2013.03.007\r\n\r\n14. Coutinho, M.F., Matos, L., Santos, J.I., and Alves, S. (2019). RNA Therapeutics: How Far Have We Gone?.\u00a0Advances in experimental medicine and biology,\u00a01157, 133\u2013177. https://doi.org/10.1007/978-3-030-19966-1_7\r\n\r\n15. Okazaki, Y., Furuno, M., Kasukawa, T., Adachi, J., Bono, H., Kondo, S., Nikaido, I., Osato, N., Saito, R., Suzuki, H., Yamanaka, I., Kiyosawa, H., Yagi, K., Tomaru, Y., Hasegawa, Y., Nogami, A., Sch\u00f6nbach, C., Gojobori, T., Baldarelli, R., Hill, D.P., \u2026 RIKEN Genome Exploration Research Group Phase I & II Team (2002). Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.\u00a0Nature,\u00a0420(6915), 563\u2013573. https://doi.org/10.1038/nature01266\r\n\r\n16. Kapranov, P., Cheng, J., Dike, S., Nix, D. A., Duttagupta, R., Willingham, A. T., Stadler, P. F., Hertel, J., Hackerm\u00fcller, J., Hofacker, I. L., Bell, I., Cheung, E., Drenkow, J., Dumais, E., Patel, S., Helt, G., Ganesh, M., Ghosh, S., Piccolboni, A., Sementchenko, V., \u2026 Gingeras, T.R. (2007). RNA maps reveal new RNA classes and a possible function for pervasive transcription.\u00a0Science (New York, N.Y.),\u00a0316(5830), 1484\u20131488. https://doi.org/10.1126/science.1138341\r\n\r\n17. Engreitz, J.M., Haines, J.E., Perez, E.M., Munson, G., Chen, J., Kane, M., McDonel, P.E., Guttman, M., and Lander, E.S. (2016). Local regulation of gene expression by lncRNA promoters, transcription and splicing.\u00a0Nature,\u00a0539(7629), 452\u2013455. https://doi.org/10.1038/nature20149\r\n\r\n18. Ebisuya, M., Yamamoto, T., Nakajima, M., and Nishida, E. (2008). Ripples from neighbouring transcription.\u00a0Nature cell biology,\u00a010(9), 1106\u20131113. https://doi.org/10.1038/ncb177\r\n\r\n19. Hurst, L. D., P\u00e1l, C., and Lercher, M.J. (2004). The evolutionary dynamics of eukaryotic gene order.\u00a0Nature reviews. Genetics,\u00a05(4), 299\u2013310. https://doi.org/10.1038/nrg1319\r\n\r\n20. Purmann, A., Toedling, J., Schueler, M., Carninci, P., Lehrach, H., Hayashizaki, Y., Huber, W., and Sperling, S. (2007). Genomic organization of transcriptomes in mammals: Coregulation and cofunctionality.\u00a0Genomics,\u00a089(5), 580\u2013587. https://doi.org/10.1016/j.ygeno.2007.01.010\r\n\r\n21. Sproul, D., Gilbert, N., and Bickmore, W.A. (2005). The role of chromatin structure in regulating the expression of clustered genes.\u00a0Nature reviews. Genetics,\u00a06(10), 775\u2013781. https://doi.org/10.1038/nrg1688\u2028\u2028\r\n\r\n22. Lee, M.P., DeBaun, M.R., Mitsuya, K., Galonek, H.L., Brandenburg, S., Oshimura, M., and Feinberg, A.P. (1999). Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a096(9), 5203\u20135208. https://doi.org/10.1073/pnas.96.9.5203\r\n\r\n23. Mabb, A.M., Judson, M.C., Zylka, M.J., and Philpot, B.D. (2011). Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes.\u00a0Trends in neurosciences,\u00a034(6), 293\u2013303. https://doi.org/10.1016/j.tins.2011.04.001\r\n\r\n22. Wevrick, R., Kerns, J.A., and Francke, U. (1994). Identification of a novel paternally expressed gene in the Prader-Willi syndrome region.\u00a0Human molecular genetics,\u00a03(10), 1877\u20131882. https://doi.org/10.1093/hmg/3.10.1877\r\n\r\n23. Kanduri, C. (2016). Long noncoding RNAs: Lessons from genomic imprinting.\u00a0Biochimica et biophysica acta,\u00a01859(1), 102\u2013111. https://doi.org/10.1016/j.bbagrm.2015.05.006\r\n\r\n24. Kurzrock, R., Kantarjian, H.M., Druker, B.J., and Talpaz, M. (2003). Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics.\u00a0Annals of internal medicine,\u00a0138(10), 819\u2013830. https://doi.org/10.7326/0003-4819-138-10-200305200-00010\r\n\r\n25. Metzeler, K.H., and Bloomfield, C.D. (2017). Clinical Relevance of RUNX1 and CBFB Alterations in Acute Myeloid Leukemia and Other Hematological Disorders.\u00a0Advances in experimental medicine and biology,\u00a0962, 175\u2013199. https://doi.org/10.1007/978-981-10-3233-2_12\u2028\u202826. \r\n\r\n26. Yu, N. Y., Hallstr\u00f6m, B.M., Fagerberg, L., Ponten, F., Kawaji, H., Carninci, P., Forrest, A.R., Fantom Consortium, Hayashizaki, Y., Uhl\u00e9n, M., and Daub, C.O. (2015). Complementing tissue characterization by integrating transcriptome profiling from the Human Protein Atlas and from the FANTOM5 consortium.\u00a0Nucleic acids research,\u00a043(14), 6787\u20136798. https://doi.org/10.1093/nar/gkv608\u2028\u202827.\r\n\r\n27. Li, L., Zhang, J.A., Dose, M., Kueh, H.Y., Mosadeghi, R., Gounari, F., and Rothenberg, E.V. (2013). A far downstream enhancer for murine Bcl11b controls its T-cell specific expression.\u00a0Blood,\u00a0122(6), 902\u2013911. https://doi.org/10.1182/blood-2012-08-447839\u2028\u202828. \r\n\r\n28. Engreitz, J.M., Ollikainen, N., and Guttman, M. (2016). Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression.\u00a0Nature reviews. Molecular cell biology,\u00a017(12), 756\u2013770. https://doi.org/10.1038/nrm.2016.126\u2028\r\n\r\n29. Strehle, M., and Guttman, M. (2020). Xist drives spatial compartmentalization of DNA and protein to orchestrate initiation and maintenance of X inactivation.\u00a0Current opinion in cell biology,\u00a064, 139\u2013147. https://doi.org/10.1016/j.ceb.2020.04.009\u2028\r\n\r\n30. Brockdorff, N., Ashworth, A., Kay, G.F., Cooper, P., Smith, S., McCabe, V.M., Norris, D.P., Penny, G.D., Patel, D., and Rastan, S. (1991). Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome.\u00a0Nature,\u00a0351(6324), 329\u2013331. https://doi.org/10.1038/351329a0\r\n\r\n31. Brown, C.J., Ballabio, A., Rupert, J.L., Lafreniere, R.G., Grompe, M., Tonlorenzi, R., and Willard, H.F. (1991). A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome.\u00a0Nature,\u00a0349(6304), 38\u201344. https://doi.org/10.1038/349038a0\r\n\r\n32. Penny, G.D., Kay, G.F., Sheardown, S.A., Rastan, S., and Brockdorff, N. (1996). Requirement for Xist in X chromosome inactivation.\u00a0Nature,\u00a0379(6561), 131\u2013137. https://doi.org/10.1038/379131a0\r\n\r\n33. Marahrens, Y., Panning, B., Dausman, J., Strauss, W., and Jaenisch, R. (1997). Xist-deficient mice are defective in dosage compensation but not spermatogenesis.\u00a0Genes & development,\u00a011(2), 156\u2013166. https://doi.org/10.1101/gad.11.2.156\r\n\r\n34. Wutz, A., and Jaenisch, R. (2000). A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation.\u00a0Molecular cell,\u00a05(4), 695\u2013705. https://doi.org/10.1016/s1097-2765(00)80248-8\r\n\r\n35. Wutz, A., Rasmussen, T.P., and Jaenisch, R. (2002). Chromosomal silencing and localization are mediated by different domains of Xist RNA.\u00a0Nature genetics,\u00a030(2), 167\u2013174. https://doi.org/10.1038/ng820\u2028\r\n\r\n36. Minajigi, A., Froberg, J., Wei, C., Sunwoo, H., Kesner, B., Colognori, D., Lessing, D., Payer, B., Boukhali, M., Haas, W., and Lee, J.T. (2015). Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science (New York, N.Y.), 349(6245), 10.1126/science.aab2276 aab2276. https://doi.org/10.1126/science.aab2276\r\n\r\n37. Barr, M.L., and Bertram, E.G. (1949). A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis.\u00a0Nature,\u00a0163(4148), 676. https://doi.org/10.1038/163676a0\r\n\r\n38. Dyer, K.A., Canfield, T.K., and Gartler, S.M. (1989). Molecular cytological differentiation of active from inactive X domains in interphase: implications for X chromosome inactivation.\u00a0\r\nCytogenetics and cell genetics,\u00a050(2-3), 116\u2013120. https://doi.org/10.1159/000132736\r\n\r\n39. Chen, C.K., Blanco, M., Jackson, C., Aznauryan, E., Ollikainen, N., Surka, C., Chow, A., Cerase, A., McDonel, P., & Guttman, M. (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing.\u00a0Science (New York, N.Y.),\u00a0354(6311), 468\u2013472. https://doi.org/10.1126/science.aae0047\r\n\r\n40. Chaumeil, J., Le Baccon, P., Wutz, A., and Heard, E. (2006). A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced.\u00a0Genes & development,\u00a020(16), 2223\u20132237. https://doi.org/10.1101/gad.380906\r\n\r\n41. Nozawa, R.S., Nagao, K., Igami, K.T., Shibata, S., Shirai, N., Nozaki, N., Sado, T., Kimura, H., and Obuse, C. (2013). Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HbiX1 pathway.\u00a0Nature structural & molecular biology,\u00a020(5), 566\u2013573. https://doi.org/10.1038/nsmb.2532\r\n\r\n42. Giorgetti, L., Lajoie, B.R., Carter, A.C., Attia, M., Zhan, Y., Xu, J., Chen, C.J., Kaplan, N., Chang, H.Y., Heard, E., and Dekker, J. (2016). Structural organization of the inactive X chromosome in the mouse.\u00a0Nature,\u00a0535(7613), 575\u2013579. https://doi.org/10.1038/nature18589\r\n\r\n43. Gdula, M.R., Nesterova, T.B., Pintacuda, G., Godwin, J., Zhan, Y., Ozadam, H., McClellan, M., Moralli, D., Krueger, F., Green, C.M., Reik, W., Kriaucionis, S., Heard, E., Dekker, J., and Brockdorff, N. (2019). The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalization on the inactive X chromosome.\u00a0Nature communications,\u00a010(1), 30. https://doi.org/10.1038/s41467-018-07907-2\r\n\r\n44. Wang, C. Y., J\u00e9gu, T., Chu, H. P., Oh, H. J., and Lee, J. T. (2018). SMCHD1 Merges Chromosome Compartments and Assists Formation of Super-Structures on the Inactive X.\u00a0Cell,\u00a0174(2), 406\u2013421.e25. https://doi.org/10.1016/j.cell.2018.05.007\r\n\r\n45. Nora, E.P., Lajoie, B.R., Schulz, E.G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N.L., Meisig, J., Sedat, J., Gribnau, J., Barillot, E., Bl\u00fcthgen, N., Dekker, J., & Heard, E. (2012). Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature,\u00a0485(7398), 381\u2013385. https://doi.org/10.1038/nature11049\r\n\r\n46. Brown, C.J., and Willard, H.F. (1994). The human X-inactivation centre is not required for maintenance of X-chromosome inactivation.\u00a0Nature,\u00a0368(6467), 154\u2013156. https://doi.org/10.1038/368154a0\r\n\r\n47. Su, H., Liu, Y., and Zhao, X. (2015). Split End Family RNA Binding Proteins: Novel Tumor Suppressors Coupling Transcriptional Regulation with RNA Processing. Cancer Translational Medicine, 1, 21-25.\r\n\r\n\u202848. Maier, D. (2019). The evolution of transcriptional repressors in the Notch signaling pathway: a computational analysis.\u00a0Hereditas,\u00a0156, 5. https://doi.org/10.1186/s41065-019-0081-0\r\n\r\n49. Kuroda, K., Han, H., Tani, S., Tanigaki, K., Tun, T., Furukawa, T., Taniguchi, Y., Kurooka, H., Hamada, Y., Toyokuni, S., and Honjo, T. (2003). Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway.\u00a0Immunity,\u00a018(2), 301\u2013312. https://doi.org/10.1016/s1074-7613(03)00029-3\r\n\r\n50. Dossin, F., Pinheiro, I., \u017bylicz, J.J., Roensch, J., Collombet, S., Le Saux, A., Chelmicki, T., Attia, M., Kapoor, V., Zhan, Y., Dingli, F., Loew, D., Mercher, T., Dekker, J., and Heard, E. (2020). SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature,\u00a0578(7795), 455\u2013460. https://doi.org/10.1038/s41586-020-1974-9\r\n\r\n51. Tamura, K., Taniguchi, Y., Minoguchi, S., Sakai, T., Tun, T., Furukawa, T., and Honjo, T. (1995). Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).\u00a0Current biology : CB,\u00a05(12), 1416\u20131423. https://doi.org/10.1016/s0960-9822(95)00279-x\r\n\r\n52. Taniguchi, Y., Furukawa, T., Tun, T., Han, H., and Honjo, T. (1998). LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein. Molecular and cellular biology,\u00a018(1), 644\u2013654. https://doi.org/10.1128/mcb.18.1.644\r\n\r\n53. Oswald, F., Kostezka, U., Astrahantseff, K., Bourteele, S., Dillinger, K., Zechner, U., Ludwig, L., Wilda, M., Hameister, H., Kn\u00f6chel, W., Liptay, S., and Schmid, R. M. (2002). SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway.\u00a0The EMBO journal,\u00a021(20), 5417\u20135426. https://doi.org/10.1093/emboj/cdf549\r\n\r\n54. Shi, Y., Downes, M., Xie, W., Kao, H.Y., Ordentlich, P., Tsai, C.C., Hon, M., & Evans, R.M. (2001). Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes & development,\u00a015(9), 1140\u20131151. https://doi.org/10.1101/gad.871201\r\n\r\n55. Lu, Z., Zhang, Q.C., Lee, B., Flynn, R.A., Smith, M.A., Robinson, J.T., Davidovich, C., Gooding, A.R., Goodrich, K.J., Mattick, J.S., Mesirov, J.P., Cech, T.R., and Chang, H.Y. (2016). RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure.\u00a0Cell,\u00a0165(5), 1267\u20131279. https://doi.org/10.1016/j.cell.2016.04.028\r\n\r\n56. Engreitz, J.M., Pandya-Jones, A., McDonel, P., Shishkin, A., Sirokman, K., Surka, C., Kadri, S., Xing, J., Goren, A., Lander, E.S., Plath, K., and Guttman, M. (2013). The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome.\u00a0Science (New York, N.Y.),\u00a0341(6147), 1237973. https://doi.org/10.1126/science.1237973\r\n\r\n57. Smilinich, N.J., Day, C.D., Fitzpatrick, G.V., Caldwell, G.M., Lossie, A.C., Cooper, P.R., Smallwood, A.C., Joyce, J.A., Schofield, P.N., Reik, W., Nicholls, R.D., Weksberg, R., Driscoll, D.J., Maher, E.R., Shows, T.B., and Higgins, M.J. (1999). A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a096(14), 8064\u20138069. https://doi.org/10.1073/pnas.96.14.8064\r\n\r\n58. Mancini-Dinardo, D., Steele, S.J., Levorse, J.M., Ingram, R.S., and Tilghman, S.M. (2006). Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes.\u00a0Genes & development,\u00a020(10), 1268\u20131282. https://doi.org/10.1101/gad.1416906\r\n\r\n59. Mohammad, F., Mondal, T., Guseva, N., Pandey, G.K., and Kanduri, C. (2010). Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development (Cambridge, England),\u00a0137(15), 2493\u20132499. https://doi.org/10.1242/dev.048181\r\n\r\n60. Mohammad, F., Pandey, G.K., Mondal, T., Enroth, S., Redrup, L., Gyllensten, U., and Kanduri, C. (2012). Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing.\u00a0Development (Cambridge, England),\u00a0139(15), 2792\u20132803. https://doi.org/10.1242/dev.079566\r\n\r\n61. Umlauf, D., Goto, Y., Cao, R., Cerqueira, F., Wagschal, A., Zhang, Y., and Feil, R. (2004). Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes.\u00a0Nature genetics,\u00a036(12), 1296\u20131300. https://doi.org/10.1038/ng1467\r\n\r\n62. Fitzpatrick, G.V., Soloway, P.D., and Higgins, M.J. (2002). Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1.\u00a0Nature genetics,\u00a032(3), 426\u2013431. https://doi.org/10.1038/ng988\r\n\r\n63. Weksberg, R., Shuman, C., and Beckwith, J.B. (2010). Beckwith-Wiedemann syndrome.\u00a0European journal of human genetics : EJHG,\u00a018(1), 8\u201314. https://doi.org/10.1038/ejhg.2009.106\r\n\r\n64. Bassett, A.R., Akhtar, A., Barlow, D.P., Bird, A.P., Brockdorff, N., Duboule, D., Ephrussi, A., Ferguson-Smith, A.C., Gingeras, T.R., Haerty, W., Higgs, D.R., Miska, E.A., and Ponting, C.P. (2014). Considerations when investigating lncRNA function in vivo.\u00a0eLife,\u00a03, e03058. https://doi.org/10.7554/eLife.03058\r\n\r\n65. Zhang, H., Zeitz, M.J., Wang, H., Niu, B., Ge, S., Li, W., Cui, J., Wang, G., Qian, G., Higgins, M.J., Fan, X., Hoffman, A.R., and Hu, J.F. (2014). Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus.\u00a0The Journal of cell biology,\u00a0204(1), 61\u201375. https://doi.org/10.1083/jcb.201304152\r\n\r\n66. Thakur, N., Kanduri, M., Holmgren, C., Mukhopadhyay, R., and Kanduri, C. (2003). Bidirectional silencing and DNA methylation-sensitive methylation-spreading properties of the Kcnq1 imprinting control region map to the same regions.\u00a0The Journal of biological chemistry,\u00a0278(11), 9514\u20139519. https://doi.org/10.1074/jbc.M212203200\r\n\r\n67. Kanduri, C., Thakur, N., and Pandey, R.R. (2006). The length of the transcript encoded from the Kcnq1ot1 antisense promoter determines the degree of silencing.\u00a0The EMBO journal,\u00a025(10), 2096\u20132106. https://doi.org/10.1038/sj.emboj.7601090\r\n\r\n68. Pandey, R.R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini-Dinardo, D., and Kanduri, C. (2008). Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation.\u00a0Molecular cell,\u00a032(2), 232\u2013246. https://doi.org/10.1016/j.molcel.2008.08.022\r\n\r\n69. Mohammad, F., Pandey, R.R., Nagano, T., Chakalova, L., Mondal, T., Fraser, P., and Kanduri, C. (2008). Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region.\u00a0Molecular and cellular biology,\u00a028(11), 3713\u20133728. https://doi.org/10.1128/MCB.02263-07\r\n\r\n70. Vigushin, D.M., Ali, S., Pace, P.E., Mirsaidi, N., Ito, K., Adcock, I., and Coombes, R.C. (2001). Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.\u00a0Clinical cancer research : an official journal of the American Association for Cancer Research,\u00a07(4), 971\u2013976.\r\n\r\n71. Cho, S.W., Kim, S., Kim, J.M., and Kim, J.S. (2013). Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease.\u00a0Nature biotechnology,\u00a031(3), 230\u2013232. https://doi.org/10.1038/nbt.2507\r\n\r\n72. Lin, Y., Protter, D.S., Rosen, M.K., and Parker, R. (2015). Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins.\u00a0Molecular cell,\u00a060(2), 208\u2013219. https://doi.org/10.1016/j.molcel.2015.08.018\r\n\r\n73. Banani, S.F., Rice, A.M., Peeples, W.B., Lin, Y., Jain, S., Parker, R., and Rosen, M.K. (2016). Compositional Control of Phase-Separated Cellular Bodies.\u00a0Cell,\u00a0166(3), 651\u2013663. https://doi.org/10.1016/j.cell.2016.06.010\r\n\r\n74. Alberti, S., Saha, S., Woodruff, J.B., Franzmann, T.M., Wang, J., and Hyman, A.A. (2018). A User's Guide for Phase Separation Assays with Purified Proteins.\u00a0Journal of molecular biology,\u00a0430(23), 4806\u20134820. https://doi.org/10.1016/j.jmb.2018.06.038\r\n\r\n75. Mancini-DiNardo, D., Steele, S.J., Ingram, R.S., and Tilghman, S.M. (2003). A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer. Human molecular genetics,\u00a012(3), 283\u2013294. https://doi.org/10.1093/hmg/ddg024\r\n\r\n76. Quinodoz, S.A., Ollikainen, N., Tabak, B., Palla, A., Schmidt, J. M., Detmar, E., Lai, M.M., Shishkin, A.A., Bhat, P., Takei, Y., Trinh, V., Aznauryan, E., Russell, P., Cheng, C., Jovanovic, M., Chow, A., Cai, L., McDonel, P., Garber, M., and Guttman, M. (2018). Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus.\u00a0Cell,\u00a0174(3), 744\u2013757.e24. https://doi.org/10.1016/j.cell.2018.05.024\r\n\r\n77. Van Nostrand, E.L., Pratt, G.A., Shishkin, A.A., Gelboin-Burkhart, C., Fang, M.Y., Sundararaman, B., Blue, S.M., Nguyen, T.B., Surka, C., Elkins, K., Stanton, R., Rigo, F., Guttman, M., and Yeo, G.W. (2016). Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).\u00a0Nature methods,\u00a013(6), 508\u2013514. https://doi.org/10.1038/nmeth.3810\r\n\r\n\u202878. Bolger, A.M., Lohse, M., and Usadel, B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data.\u00a0Bioinformatics (Oxford, England),\u00a030(15), 2114\u20132120. https://doi.org/10.1093/bioinformatics/btu170\u2028\u202879.\r\n\r\n79. Dobin, A., Davis, C.A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., and Gingeras, T. R. (2013). STAR: ultrafast universal RNA-seq aligner.\u00a0Bioinformatics (Oxford, England),\u00a029(1), 15\u201321. https://doi.org/10.1093/bioinformatics/bts635\u2028\u202880. \r\n\r\n80. Quinodoz, S.A., Bhat, P., Ollikainen, N., Jachowicz, J., Banerjee, A.K., Chovanec, P., Blanco, M.R., Chow, A., Markaki, Y., Plath, K. and Guttman, M. (2020). RNA promotes the formation of spatial compartments in the nucleus. bioRxiv 2020.08.25.267435; doi: https://doi.org/10.1101/2020.08.25.267435\u2028\u202881. \r\n\r\n81. Shishkin, A.A., Giannoukos, G., Kucukural, A., Ciulla, D., Busby, M., Surka, C., Chen, J., Bhattacharyya, R.P., Rudy, R.F., Patel, M.M., Novod, N., Hung, D.T., Gnirke, A., Garber, M., Guttman, M., and Livny, J. (2015). Simultaneous generation of many RNA-seq libraries in a single reaction.\u00a0Nature methods,\u00a012(4), 323\u2013325. https://doi.org/10.1038/nmeth.3313\u2028\u202882. \r\n\r\n82. Kechin, A., Boyarskikh, U., Kel, A., and Filipenko, M. (2017). cutPrimers: A New Tool for Accurate Cutting of Primers from Reads of Targeted Next Generation Sequencing.\u00a0Journal of computational biology : a journal of computational molecular cell biology,\u00a024(11), 1138\u20131143. https://doi.org/10.1089/cmb.2017.0096\u2028\r\n\r\n83. Jin, Y., Tam, O.H., Paniagua, E., and Hammell, M. (2015). Tetranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets.\u00a0Bioinformatics (Oxford, England),\u00a031(22), 3593\u20133599. https://doi.org/10.1093/bioinformatics/btv422\u2028\u202884. \r\n\r\n84. Langmead, B., and Salzberg, S.L. (2012). Fast gapped-read alignment with Bowtie 2.\u00a0Nature methods,\u00a09(4), 357\u2013359. https://doi.org/10.1038/nmeth.1923\u2028\u202885.\r\n\r\n85. Krueger, F., and Andrews, S.R. (2016). SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes.\u00a0F1000Research,\u00a05, 1479. https://doi.org/10.12688/f1000research.9037.2\r\n\r\n86. Smit, A., Hubley, R., and Grenn, P. RepeatMasker Open-4.0. RepeatMasker Open-4.0.7. (2015).\r\n\r\n87. Quinlan, A.R., and Hall, I.M. (2010). BEDTools: a flexible suite of utilities for comparing genomic features.\u00a0Bioinformatics (Oxford, England),\u00a026(6), 841\u2013842. https://doi.org/10.1093/bioinformatics/btq033\u2028\r\n\r\n88. Ewels, P., Magnusson, M., Lundin, S., and K\u00e4ller, M. (2016). MultiQC: summarize analysis results for multiple tools and samples in a single report.\u00a0Bioinformatics (Oxford, England), 32(19), 3047\u20133048. https://doi.org/10.1093/bioinformatics/btw354\r\n\r\n\u202889. Kuehn, M. R., Bradley, A., Robertson, E. J., & Evans, M. J. (1987). A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.\u00a0Nature,\u00a0326(6110), 295\u2013298. https://doi.org/10.1038/326295a0\r\n\r\n90. Baron-Benhamou, J., Gehring, N.H., Kulozik, A.E., and Hentze, M.W. (2004). Using the lambdaN peptide to tether proteins to RNAs.\u00a0Methods in molecular biology (Clifton, N.J.),\u00a0257, 135\u2013154. https://doi.org/10.1385/1-59259-750-5:135\r\n\r\n\u202891. Zhao, S., Jiang, E., Chen, S., Gu, Y., Shangguan, A. J., Lv, T., Luo, L., and Yu, Z. (2016). PiggyBac transposon vectors: the tools of the human gene encoding.\u00a0Translational lung cancer research,\u00a05(1), 120\u2013125. https://doi.org/10.3978/j.issn.2218-6751.2016.01.05\u2028\u202892. \r\n\r\n92. Halpern, M.E., Rhee, J., Goll, M.G., Akitake, C.M., Parsons, M., and Leach, S.D. (2008). Gal4/UAS transgenic tools and their application to zebrafish.\u00a0Zebrafish,\u00a05(2), 97\u2013110. https://doi.org/10.1089/zeb.2008.0530", "Chapter 4: \r\n\r\n1. Yui, M.A., and Rothenberg, E.V. (2014). Developmental gene networks: a triathlon on the course to T cell identity.\u00a0Nature reviews. Immunology,\u00a014(8), 529\u2013545. https://doi.org/10.1038/nri3702\r\n\r\n2. Radtke, F., Wilson, A., Stark, G., Bauer, M., van Meerwijk, J., MacDonald, H.R., and Aguet, M. (1999). Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity,\u00a010(5), 547\u2013558. https://doi.org/10.1016/s1074-7613(00)80054-0\r\n\r\n3. Previs, R.A., Coleman, R.L., Harris, A.L., and Sood, A.K. (2015). Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer.\u00a0Clinical cancer research : an official journal of the American Association for Cancer Research,\u00a021(5), 955\u2013961. https://doi.org/10.1158/1078-0432.CCR-14-0809\r\n\r\n4. Ntziachristos, P., Lim, J.S., Sage, J., and Aifantis, I. (2014). From fly wings to targeted cancer therapies: a centennial for notch signaling.\u00a0Cancer cell,\u00a025(3), 318\u2013334. https://doi.org/10.1016/j.ccr.2014.02.018\r\n\r\n5. Dexter, J.S. (1914). The analysis of continuous variation in Drosophila by a study of its linkage relations. Am Nat 48, 712-758.\r\n\r\n6. Tanigaki, K., and Honjo, T. (2007). Regulation of lymphocyte development by Notch signaling.\u00a0Nature immunology,\u00a08(5), 451\u2013456. https://doi.org/10.1038/ni1453\r\n\r\n7. Tamura, K., Taniguchi, Y., Minoguchi, S., Sakai, T., Tun, T., Furukawa, T., and Honjo, T. (1995). Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H).\u00a0Current biology : CB,\u00a05(12), 1416\u20131423. https://doi.org/10.1016/s0960-9822(95)00279-x\r\n\r\n8. Taniguchi, Y., Furukawa, T., Tun, T., Han, H., and Honjo, T. (1998). LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein.\u00a0Molecular and cellular biology,\u00a018(1), 644\u2013654. https://doi.org/10.1128/mcb.18.1.644\r\n\r\n9. Oswald, F., Kostezka, U., Astrahantseff, K., Bourteele, S., Dillinger, K., Zechner, U., Ludwig, L., Wilda, M., Hameister, H., Kn\u00f6chel, W., Liptay, S., and Schmid, R.M. (2002). SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway.\u00a0The EMBO journal,\u00a021(20), 5417\u20135426. https://doi.org/10.1093/emboj/cdf549\r\n\r\n10. Newberry, E.P., Latifi, T., and Towler, D.A. (1999). The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter. Biochemistry, 38(33), 10678\u201310690. https://doi.org/10.1021/bi990967j\r\n\r\n11. Su, H., Liu, Y., and Zhao, X. (2015). Split End Family RNA Binding Proteins: Novel Tumor Suppressors Coupling Transcriptional Regulation with RNA Processing. Cancer Translational Medicine, 1, 21-25.\r\n\r\n12. Shi, Y., Downes, M., Xie, W., Kao, H.Y., Ordentlich, P., Tsai, C.C., Hon, M., and Evans, R.M. (2001). Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes & development,\u00a015(9), 1140\u20131151. https://doi.org/10.1101/gad.871201\r\n\r\n13. Dossin, F., Pinheiro, I., \u017bylicz, J.J., Roensch, J., Collombet, S., Le Saux, A., Chelmicki, T., Attia, M., Kapoor, V., Zhan, Y., Dingli, F., Loew, D., Mercher, T., Dekker, J., and Heard, E. (2020). SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature, 578(7795), 455\u2013460. https://doi.org/10.1038/s41586-020-1974-9\r\n\r\n14. Osborne, B.A., and Minter, L.M. (2007). Notch signalling during peripheral T-cell activation and differentiation.\u00a0Nature reviews. Immunology,\u00a07(1), 64\u201375. https://doi.org/10.1038/nri1998\r\n\r\n15. Tsuji, M., Shinkura, R., Kuroda, K., Yabe, D., and Honjo, T. (2007). Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0104(5), 1610\u20131615. https://doi.org/10.1073/pnas.0610520104\r\n\r\n16. Kuroda, K., Han, H., Tani, S., Tanigaki, K., Tun, T., Furukawa, T., Taniguchi, Y., Kurooka, H., Hamada, Y., Toyokuni, S., and Honjo, T. (2003). Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway.\u00a0Immunity,\u00a018(2), 301\u2013312. https://doi.org/10.1016/s1074-7613(03)00029-3\r\n\r\n17. Pui, J.C., Allman, D., Xu, L., DeRocco, S., Karnell, F.G., Bakkour, S., Lee, J.Y., Kadesch, T., Hardy, R.R., Aster, J.C., and Pear, W.S. (1999). Notch1 expression in early lymphopoiesis influences B versus T lineage determination.\u00a0Immunity,\u00a011(3), 299\u2013308. https://doi.org/10.1016/s1074-7613(00)80105-3\r\n\r\n18. Holmes, R., and Z\u00fa\u00f1iga-Pfl\u00fccker, J.C. (2009). The OP9-DL1 system: generation of T-lymphocytes from embryonic or hematopoietic stem cells in vitro.\u00a0Cold Spring Harbor protocols,\u00a02009(2), pdb.prot5156. https://doi.org/10.1101/pdb.prot5156\r\n\r\n19. Godfrey, D.I., and Zlotnik, A. (1993). Control points in early T-cell development. Immunology today,\u00a014(11), 547\u2013553. https://doi.org/10.1016/0167-5699(93)90186-O\r\n\r\n20. Dionne, C.J., Tse, K.Y., Weiss, A.H., Franco, C.B., Wiest, D.L., Anderson, M.K., and Rothenberg, E.V. (2005). Subversion of T lineage commitment by PU.1 in a clonal cell line system.\u00a0Developmental biology,\u00a0280(2), 448\u2013466. https://doi.org/10.1016/j.ydbio.2005.01.027\r\n\r\n21. Adler, S.H., Chiffoleau, E., Xu, L., Dalton, N.M., Burg, J.M., Wells, A.D., Wolfe, M.S., Turka, L.A., and Pear, W.S. (2003). Notch signaling augments T cell responsiveness by enhancing CD25 expression.\u00a0Journal of immunology (Baltimore, Md. : 1950),\u00a0171(6), 2896\u20132903. https://doi.org/10.4049/jimmunol.171.6.2896\r\n\r\n22. Bellavia, D., Campese, A.F., Alesse, E., Vacca, A., Felli, M.P., Balestri, A., Stoppacciaro, A., Tiveron, C., Tatangelo, L., Giovarelli, M., Gaetano, C., Ruco, L., Hoffman, E. S., Hayday, A.C., Lendahl, U., Frati, L., Gulino, A., and Screpanti, I. (2000). Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3 transgenic mice.\u00a0The EMBO journal,\u00a019(13), 3337\u20133348. https://doi.org/10.1093/emboj/19.13.3337\r\n\r\n23. Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., & Kintner, C. (2001). Nrarp is a novel intracellular component of the Notch signaling pathway.\u00a0Genes & development,\u00a015(15), 1885\u20131899. https://doi.org/10.1101/gad.908101\r\n\r\n24. Jarrett, S.M., Seegar, T., Andrews, M., Adelmant, G., Marto, J.A., Aster, J.C., and Blacklow, S.C. (2019). Extension of the Notch intracellular domain ankyrin repeat stack by NRARP promotes feedback inhibition of Notch signaling.\u00a0Science signaling,\u00a012(606), eaay2369. https://doi.org/10.1126/scisignal.aay2369\r\n\r\n25. Yun, T.J., and Bevan, M.J. (2003). Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1 signaling pathways involved in T cell development.\u00a0Journal of immunology (Baltimore, Md. : 1950),\u00a0170(12), 5834\u20135841. https://doi.org/10.4049/jimmunol.170.12.5834\r\n\r\n26. McHugh, C.A., Chen, C.K., Chow, A., Surka, C. F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M.J., Shishkin, A.A., Su, J., Lander, E.S., Hess, S., Plath, K., and Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.\u00a0Nature,\u00a0521(7551), 232\u2013236. https://doi.org/10.1038/nature14443\r\n\r\n27. Chu, C., Zhang, Q.C., da Rocha, S. T., Flynn, R.A., Bharadwaj, M., Calabrese, J.M., Magnuson, T., Heard, E., and Chang, H.Y. (2015). Systematic discovery of Xist RNA binding proteins.\u00a0Cell,\u00a0161(2), 404\u2013416. https://doi.org/10.1016/j.cell.2015.03.025\r\n\r\n28. Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T.B., and Brockdorff, N. (2015). A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.\u00a0Cell reports,\u00a012(4), 562\u2013572. https://doi.org/10.1016/j.celrep.2015.06.053\r\n\r\n29. Monfort, A., Di Minin, G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., and Wutz, A. (2015). Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.\u00a0Cell reports,\u00a012(4), 554\u2013561. https://doi.org/10.1016/j.celrep.2015.06.067\r\n\r\n30. Wollerton, M.C., Gooding, C., Wagner, E.J., Garcia-Blanco, M.A., & Smith, C.W. (2004). Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay.\u00a0Molecular cell,\u00a013(1), 91\u2013100. https://doi.org/10.1016/s1097-2765(03)00502-1\r\n\r\n31. Jumaa, H., and Nielsen, P.J. (2000). Regulation of SRp20 exon 4 splicing.\u00a0Biochimica et biophysica acta,\u00a01494(1-2), 137\u2013143. https://doi.org/10.1016/s0167-4781(00)00233-5\r\n\r\n32. Ottens, F., and Gehring, N.H. (2016). Physiological and pathophysiological role of nonsense-mediated mRNA decay.\u00a0Pflugers Archiv : European journal of physiology,\u00a0468(6), 1013\u20131028. https://doi.org/10.1007/s00424-016-1826-5\r\n\r\n33. Rossbach, O., Hung, L.H., Schreiner, S., Grishina, I., Heiner, M., Hui, J., and Bindereif, A. (2009). Auto- and cross-regulation of the hnRNP L proteins by alternative splicing.\u00a0Molecular and cellular biology,\u00a029(6), 1442\u20131451. https://doi.org/10.1128/MCB.01689-08\r\n\r\n34. Boelens, W.C., Jansen, E.J., van Venrooij, W.J., Stripecke, R., Mattaj, I.W., and Gunderson, S.I. (1993). The human U1 snRNP-specific U1A protein inhibits polyadenylation of its own pre-mRNA.\u00a0Cell,\u00a072(6), 881\u2013892. https://doi.org/10.1016/0092-8674(93)90577-d\r\n\r\n35. M\u00fcller-McNicoll, M., Rossbach, O., Hui, J., and Medenbach, J. (2019). Auto-regulatory feedback by RNA-binding proteins.\u00a0Journal of molecular cell biology,\u00a011(10), 930\u2013939. https://doi.org/10.1093/jmcb/mjz043\r\n\r\n36. Malvaez, M., McQuown, S. C., Rogge, G.A., Astarabadi, M., Jacques, V., Carreiro, S., Rusche, J.R., and Wood, M.A. (2013). HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0110(7), 2647\u20132652. https://doi.org/10.1073/pnas.1213364110\r\n\r\n37. Shi, X.Y., Ding, W., Li, T. Q., Zhang, Y.X., and Zhao, S.C. (2017). Histone Deacetylase (HDAC) Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), Induces Apoptosis in Prostate Cancer Cell Lines via the Akt/FOXO3a Signaling Pathway.\u00a0Medical science monitor : international medical journal of experimental and clinical research,\u00a023, 5793\u20135802. https://doi.org/10.12659/msm.904597\r\n\r\n38. Vigushin, D.M., Ali, S., Pace, P.E., Mirsaidi, N., Ito, K., Adcock, I., and Coombes, R.C. (2001). Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo.\u00a0Clinical cancer research : an official journal of the American Association for Cancer Research,\u00a07(4), 971\u2013976.\r\n\r\n39. Reeves, G.T. (2019). The engineering principles of combining a transcriptional incoherent feedforward loop with negative feedback.\u00a0Journal of biological engineering,\u00a013, 62. https://doi.org/10.1186/s13036-019-0190-3\r\n\r\n40. Milo, R., Shen-Orr, S., Itzkovitz, S., Kashtan, N., Chklovskii, D., and Alon, U. (2002). Network motifs: simple building blocks of complex networks.\u00a0Science (New York, N.Y.),\u00a0298(5594), 824\u2013827. https://doi.org/10.1126/science.298.5594.824\r\n\r\n41. Eichenberger, P., Fujita, M., Jensen, S.T., Conlon, E.M., Rudner, D.Z., Wang, S.T., Ferguson, C., Haga, K., Sato, T., Liu, J.S., and Losick, R. (2004). The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis.\u00a0PLoS biology,\u00a02(10), e328. https://doi.org/10.1371/journal.pbio.0020328\r\n\r\n42. Mangan, S., Itzkovitz, S., Zaslaver, A., and Alon, U. (2006). The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli.\u00a0Journal of molecular biology,\u00a0356(5), 1073\u20131081. https://doi.org/10.1016/j.jmb.2005.12.003\r\n\r\n43. Lee, T.I., Rinaldi, N.J., Robert, F., Odom, D.T., Bar-Joseph, Z., Gerber, G.K., Hannett, N. M., Harbison, C.T., Thompson, C.M., Simon, I., Zeitlinger, J., Jennings, E.G., Murray, H.L., Gordon, D.B., Ren, B., Wyrick, J.J., Tagne, J.B., Volkert, T.L., Fraenkel, E., Gifford, D.K., \u2026 Young, R.A. (2002). Transcriptional regulatory networks in Saccharomyces cerevisiae.\u00a0Science (New York, N.Y.),\u00a0298(5594), 799\u2013804. https://doi.org/10.1126/science.1075090\r\n\r\n44. Boyer, L.A., Lee, T.I., Cole, M.F., Johnstone, S.E., Levine, S.S., Zucker, J.P., Guenther, M.G., Kumar, R.M., Murray, H.L., Jenner, R.G., Gifford, D.K., Melton, D.A., Jaenisch, R., and Young, R.A. (2005). Core transcriptional regulatory circuitry in human embryonic stem cells.\u00a0Cell,\u00a0122(6), 947\u2013956. https://doi.org/10.1016/j.cell.2005.08.020\r\n\r\n45. Swiers, G., Patient, R., and Loose, M. (2006). Genetic regulatory networks programming hematopoietic stem cells and erythroid lineage specification.\u00a0Developmental biology,\u00a0294(2), 525\u2013540. https://doi.org/10.1016/j.ydbio.2006.02.051\r\n\r\n46. Chevrier, N., Mertins, P., Artyomov, M.N., Shalek, A.K., Iannacone, M., Ciaccio, M.F., Gat-Viks, I., Tonti, E., DeGrace, M.M., Clauser, K.R., Garber, M., Eisenhaure, T.M., Yosef, N., Robinson, J., Sutton, A., Andersen, M.S., Root, D.E., von Andrian, U., Jones, R.B., Park, H., \u2026 Hacohen, N. (2011). Systematic discovery of TLR signaling components delineates viral-sensing circuits.\u00a0Cell,\u00a0147(4), 853\u2013867. https://doi.org/10.1016/j.cell.2011.10.022\r\n\r\n47. Johnston, R.J., Jr, Otake, Y., Sood, P., Vogt, N., Behnia, R., Vasiliauskas, D., McDonald, E., Xie, B., Koenig, S., Wolf, R., Cook, T., Gebelein, B., Kussell, E., Nakagoshi, H., and Desplan, C. (2011). Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye.\u00a0Cell,\u00a0145(6), 956\u2013968. https://doi.org/10.1016/j.cell.2011.05.003\r\n\r\n48. Krejc\u00ed, A., Bernard, F., Housden, B.E., Collins, S., and Bray, S.J. (2009). Direct response to Notch activation: signaling crosstalk and incoherent logic.\u00a0Science signaling,\u00a02(55), ra1. https://doi.org/10.1126/scisignal.2000140\r\n\r\n49. Hart, Y., and Alon, U. (2013). The utility of paradoxical components in biological circuits.\u00a0Molecular cell,\u00a049(2), 213\u2013221. https://doi.org/10.1016/j.molcel.2013.01.004\r\n\r\n50. Basu, S., Mehreja, R., Thiberge, S., Chen, M.T., and Weiss, R. (2004). Spatiotemporal control of gene expression with pulse-generating networks.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0101(17), 6355\u20136360. https://doi.org/10.1073/pnas.0307571101\r\n\r\n51. Mangan, S., and Alon, U. (2003). Structure and function of the feed-forward loop network motif.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0100(21), 11980\u201311985. https://doi.org/10.1073/pnas.2133841100\r\n\r\n52. Alon, U. (2007). Network motifs: theory and experimental approaches.\u00a0Nature reviews. Genetics,\u00a08(6), 450\u2013461. https://doi.org/10.1038/nrg2102\r\n\r\n53. Shoval, O., and Alon, U. (2010). SnapShot: network motifs.\u00a0Cell,\u00a0143(2), 326\u2013e1. https://doi.org/10.1016/j.cell.2010.09.050\r\n\r\n54. Mac\u00eda, J., Widder, S., and Sol\u00e9, R. (2009). Specialized or flexible feed-forward loop motifs: a question of topology.\u00a0BMC systems biology,\u00a03, 84. https://doi.org/10.1186/1752-0509-3-84\r\n\r\n55. Entus, R., Aufderheide, B., and Sauro, H.M. (2007). Design and implementation of three incoherent feed-forward motif based biological concentration sensors.\u00a0Systems and synthetic biology,\u00a01(3), 119\u2013128. https://doi.org/10.1007/s11693-007-9008-6\r\n\r\n56. Kaplan, S., Bren, A., Dekel, E., and Alon, U. (2008). The incoherent feed-forward loop can generate non-monotonic input functions for genes.\u00a0Molecular systems biology,\u00a04, 203. https://doi.org/10.1038/msb.2008.43\r\n\r\n57. Kim, D., Kwon, Y.K., and Cho, K.H. (2008). The biphasic behavior of incoherent feed-forward loops in biomolecular regulatory networks.\u00a0BioEssays : news and reviews in molecular, cellular and developmental biology,\u00a030(11-12), 1204\u20131211. https://doi.org/10.1002/bies.20839\r\n\r\n58. Goentoro, L., Shoval, O., Kirschner, M.W., and Alon, U. (2009). The incoherent feedforward loop can provide fold-change detection in gene regulation.\u00a0Molecular cell,\u00a036(5), 894\u2013899. https://doi.org/10.1016/j.molcel.2009.11.018\r\n\r\n59. Shoval, O., Goentoro, L., Hart, Y., Mayo, A., Sontag, E., and Alon, U. (2010). Fold-change detection and scalar symmetry of sensory input fields.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0107(36), 15995\u201316000. https://doi.org/10.1073/pnas.1002352107\r\n\r\n60. Hong, J., Brandt, N., Abdul-Rahman, F., Yang, A., Hughes, T., and Gresham, D. (2018). An incoherent feedforward loop facilitates adaptive tuning of gene expression.\u00a0eLife,\u00a07, e32323. https://doi.org/10.7554/eLife.32323\r\n\r\n61. Bleris, L., Xie, Z., Glass, D., Adadey, A., Sontag, E., and Benenson, Y. (2011). Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template.\u00a0Molecular systems biology,\u00a07, 519. https://doi.org/10.1038/msb.2011.49\r\n\r\n62. Ebert, M.S., and Sharp, P.A. (2012). Roles for microRNAs in conferring robustness to biological processes.\u00a0Cell,\u00a0149(3), 515\u2013524. https://doi.org/10.1016/j.cell.2012.04.005\r\n\r\n63. Elowitz, M.B., Levine, A.J., Siggia, E.D., and Swain, P.S. (2002). Stochastic gene expression in a single cell.\u00a0Science (New York, N.Y.),\u00a0297(5584), 1183\u20131186. https://doi.org/10.1126/science.1070919\r\n\r\n64. Blake, W.J., KAErn, M., Cantor, C.R., and Collins, J.J. (2003). Noise in eukaryotic gene expression.\u00a0Nature,\u00a0422(6932), 633\u2013637. https://doi.org/10.1038/nature01546\r\n\r\n65. Blake, W.J., Bal\u00e1zsi, G., Kohanski, M.A., Isaacs, F.J., Murphy, K.F., Kuang, Y., Cantor, C.R., Walt, D.R., and Collins, J.J. (2006). Phenotypic consequences of promoter-mediated transcriptional noise.\u00a0Molecular cell,\u00a024(6), 853\u2013865. https://doi.org/10.1016/j.molcel.2006.11.003\r\n\r\n66. Paulsson, J. (2004). Summing up the noise in gene networks.\u00a0Nature,\u00a0427(6973), 415\u2013418. https://doi.org/10.1038/nature02257\r\n\r\n67. Raser, J.M., and O'Shea, E.K. (2005). Noise in gene expression: origins, consequences, and control.\u00a0Science (New York, N.Y.),\u00a0309(5743), 2010\u20132013. https://doi.org/10.1126/science.1105891\r\n\r\n68. Newman, J.R., Ghaemmaghami, S., Ihmels, J., Breslow, D.K., Noble, M., DeRisi, J.L., and Weissman, J.S. (2006). Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise.\u00a0Nature,\u00a0441(7095), 840\u2013846. https://doi.org/10.1038/nature04785\r\n\r\n69. Sigal, A., Milo, R., Cohen, A., Geva-Zatorsky, N., Klein, Y., Liron, Y., Rosenfeld, N., Danon, T., Perzov, N., and Alon, U. (2006). Variability and memory of protein levels in human cells.\u00a0Nature,\u00a0444(7119), 643\u2013646. https://doi.org/10.1038/nature05316\r\n\r\n70. Osella, M., Bosia, C., Cor\u00e1, D., and Caselle, M. (2011). The role of incoherent microRNA-mediated feedforward loops in noise buffering.\u00a0PLoS computational biology,\u00a07(3), e1001101. https://doi.org/10.1371/journal.pcbi.1001101\r\n\r\n71. Li, X., Cassidy, J.J., Reinke, C.A., Fischboeck, S., and Carthew, R.W. (2009). A microRNA imparts robustness against environmental fluctuation during development.\u00a0Cell,\u00a0137(2), 273\u2013282. https://doi.org/10.1016/j.cell.2009.01.058\r\n\r\n72. Hornstein, E., and Shomron, N. (2006). Canalization of development by microRNAs.\u00a0Nature genetics,\u00a038 Suppl, S20\u2013S24. https://doi.org/10.1038/ng1803\r\n\r\n73. Nandagopal, N., Santat, L.A., LeBon, L., Sprinzak, D., Bronner, M.E., and Elowitz, M.B. (2018). Dynamic Ligand Discrimination in the Notch Signaling Pathway.\u00a0Cell,\u00a0172(4), 869\u2013880.e19. https://doi.org/10.1016/j.cell.2018.01.002\r\n\r\n74. Hosokawa, H., Ungerb\u00e4ck, J., Wang, X., Matsumoto, M., Nakayama, K. I., Cohen, S.M., Tanaka, T., and Rothenberg, E.V. (2018). Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.\u00a0Immunity,\u00a048(6), 1119\u20131134.e7. https://doi.org/10.1016/j.immuni.2018.04.024\r\n\r\n75. Del Real, M.M., and Rothenberg, E.V. (2013). Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3.\u00a0Development (Cambridge, England),\u00a0140(6), 1207\u20131219. https://doi.org/10.1242/dev.088559\r\n\r\n76. Kim, S.I., Oceguera-Yanez, F., Sakurai, C., Nakagawa, M., Yamanaka, S., and Woltjen, K. (2016). Inducible Transgene Expression in Human iPS Cells Using Versatile All-in-One piggyBac Transposons.\u00a0Methods in molecular biology (Clifton, N.J.),\u00a01357, 111\u2013131. https://doi.org/10.1007/7651_2015_251\r\n\r\n77. Zarnegar, M.A., Chen, J., and Rothenberg, E.V. (2010). Cell-type-specific activation and repression of PU.1 by a complex of discrete, functionally specialized cis-regulatory elements. Molecular and cellular biology,\u00a030(20), 4922\u20134939. https://doi.org/10.1128/MCB.00354-10\r\n\r\n78. Izon, D.J., Punt, J.A., Xu, L., Karnell, F.G., Allman, D., Myung, P.S., Boerth, N.J., Pui, J.C., Koretzky, G.A., and Pear, W.S. (2001). Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength.\u00a0Immunity,\u00a014(3), 253\u2013264. https://doi.org/10.1016/s1074-7613(01)00107-8\r\n\r\n79. Lai, E.C. (2004). Notch signaling: control of cell communication and cell fate.\u00a0Development (Cambridge, England),\u00a0131(5), 965\u2013973. https://doi.org/10.1242/dev.01074\r\n\r\n80. Amsen, D., Antov, A., and Flavell, R.A. (2009). The different faces of Notch in T-helper-cell differentiation.\u00a0Nature reviews. Immunology,\u00a09(2), 116\u2013124. https://doi.org/10.1038/nri2488\r\n\r\n81. Ng, K.K., Yui, M.A., Mehta, A., Siu, S., Irwin, B., Pease, S., Hirose, S., Elowitz, M.B., Rothenberg, E.V., and Kueh, H.Y. (2018). A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment.\u00a0eLife,\u00a07, e37851. https://doi.org/10.7554/eLife.37851\r\n\r\n82. Quinodoz, S.A., Bhat, P., Ollikainen, N., Jachowicz, J., Banerjee, A.K., Chovanec, P., Blanco, M.R., Chow, A., Markaki, Y., Plath, K. and Guttman, M. (2020). RNA promotes the formation of spatial compartments in the nucleus. bioRxiv 2020.08.25.267435; doi: https://doi.org/10.1101/2020.08.25.267435\r\n\r\n83. Quinodoz, S.A., Ollikainen, N., Tabak, B., Palla, A., Schmidt, J. M., Detmar, E., Lai, M.M., Shishkin, A.A., Bhat, P., Takei, Y., Trinh, V., Aznauryan, E., Russell, P., Cheng, C., Jovanovic, M., Chow, A., Cai, L., McDonel, P., Garber, M., and Guttman, M. (2018). Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus.\u00a0Cell,\u00a0174(3), 744\u2013757.e24. https://doi.org/10.1016/j.cell.2018.05.024\r\n\r\n84. Heng, T.S., Painter, M.W., and Immunological Genome Project Consortium (2008). The Immunological Genome Project: networks of gene expression in immune cells.\u00a0Nature immunology,\u00a09(10), 1091\u20131094. https://doi.org/10.1038/ni1008-1091\r\n\r\n85. Patro, R., Duggal, G., Love, M.I., Irizarry, R.A., and Kingsford, C. (2017). Salmon provides fast and bias-aware quantification of transcript expression.\u00a0Nature methods,\u00a014(4), 417\u2013419. https://doi.org/10.1038/nmeth.4197\r\n\r\n86. Jiang, H., Lei, R., Ding, S.W., and Zhu, S. (2014). Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads.\u00a0BMC bioinformatics,\u00a015, 182. https://doi.org/10.1186/1471-2105-15-182", "Chapter 5: \r\n\r\n1. Engreitz, J.M., Ollikainen, N., and Guttman, M. (2016). Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression.\u00a0Nature reviews. Molecular cell biology,\u00a017(12), 756\u2013770. https://doi.org/10.1038/nrm.2016.126\r\n\r\n2. Strehle, M., and Guttman, M. (2020). Xist drives spatial compartmentalization of DNA and protein to orchestrate initiation and maintenance of X inactivation.\u00a0Current opinion in cell biology,\u00a064, 139\u2013147. https://doi.org/10.1016/j.ceb.2020.04.009\r\n\r\n3. Smilinich, N.J., Day, C.D., Fitzpatrick, G.V., Caldwell, G.M., Lossie, A.C., Cooper, P.R., Smallwood, A.C., Joyce, J.A., Schofield, P.N., Reik, W., Nicholls, R.D., Weksberg, R., Driscoll, D.J., Maher, E.R., Shows, T.B., and Higgins, M.J. (1999). A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a096(14), 8064\u20138069. https://doi.org/10.1073/pnas.96.14.8064\u2028\u20284. \r\n\r\n4. Mancini-DiNardo, D., Steele, S.J., Ingram, R.S., and Tilghman, S.M. (2003). A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer.\u00a0Human molecular genetics,\u00a012(3), 283\u2013294. https://doi.org/10.1093/hmg/ddg024\r\n\r\n5. Verberne, E.A., Goh, S., England, J., van Ginkel, M., Rafael-Croes, L., Maas, S., Polstra, A., Zarate, Y.A., Bosanko, K.A., Pechter, K.B., Bedoukian, E., Izumi, K., Chaudhry, A., Robin, N.H., Boothe, M., Lippa, N.C., Aggarwal, V., De Vivo, D.C., Lehman, A., Study, C., \u2026 Campeau, P.M. (2020). JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.\u00a0Genetics in medicine : official journal of the American College of Medical Genetics, 10.1038/s41436-020-00992-z. Advance online publication. https://doi.org/10.1038/s41436-020-00992-z\r\n\r\n6. Ge, Y., Schuster, M.B., Pundhir, S., Rapin, N., Bagger, F.O., Sidiropoulos, N., Hashem, N., and Porse, B.T. (2019). The splicing factor RBM25 controls MYC activity in acute myeloid leukemia.\u00a0Nature communications,\u00a010(1), 172. https://doi.org/10.1038/s41467-018-08076-y\r\n\r\n7. Kim, H., Kang, K., Ekram, M.B., Roh, T.Y., and Kim, J. (2011). Aebp2 as an epigenetic regulator for neural crest cells.\u00a0PloS one,\u00a06(9), e25174. https://doi.org/10.1371/journal.pone.0025174\r\n\r\n8. M\u00fcller-McNicoll, M., Rossbach, O., Hui, J., and Medenbach, J. (2019). Auto-regulatory feedback by RNA-binding proteins.\u00a0Journal of molecular cell biology,\u00a011(10), 930\u2013939. https://doi.org/10.1093/jmcb/mjz043\r\n\r\n9. Kuroda, K., Han, H., Tani, S., Tanigaki, K., Tun, T., Furukawa, T., Taniguchi, Y., Kurooka, H., Hamada, Y., Toyokuni, S., and Honjo, T. (2003). Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway.\u00a0Immunity,\u00a018(2), 301\u2013312. https://doi.org/10.1016/s1074-7613(03)00029-3\r\n\r\n10. Yabe, D., Fukuda, H., Aoki, M., Yamada, S., Takebayashi, S., Shinkura, R., Yamamoto, N., & Honjo, T. (2007). Generation of a conditional knockout allele for mammalian Spen protein Mint/SHARP.\u00a0Genesis (New York, N.Y. : 2000),\u00a045(5), 300\u2013306. https://doi.org/10.1002/dvg.20296\r\n\r\n11. Lamar, E., Deblandre, G., Wettstein, D., Gawantka, V., Pollet, N., Niehrs, C., & Kintner, C. (2001). Nrarp is a novel intracellular component of the Notch signaling pathway.\u00a0Genes & development,\u00a015(15), 1885\u20131899. https://doi.org/10.1101/gad.908101\r\n\r\n\u202812. Reeves, G.T. (2019). The engineering principles of combining a transcriptional incoherent feedforward loop with negative feedback.\u00a0Journal of biological engineering,\u00a013, 62. https://doi.org/10.1186/s13036-019-0190-3\u2028\r\n\r\n13. Basu, S., Mehreja, R., Thiberge, S., Chen, M.T., and Weiss, R. (2004). Spatiotemporal control of gene expression with pulse-generating networks.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0101(17), 6355\u20136360. https://doi.org/10.1073/pnas.0307571101\r\n\r\n14. Mangan, S., and Alon, U. (2003). Structure and function of the feed-forward loop network motif.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0100(21), 11980\u201311985. https://doi.org/10.1073/pnas.2133841100\r\n\r\n15. Mangan, S., Itzkovitz, S., Zaslaver, A., and Alon, U. (2006). The incoherent feed-forward loop accelerates the response-time of the gal system of Escherichia coli.\u00a0Journal of molecular biology,\u00a0356(5), 1073\u20131081. https://doi.org/10.1016/j.jmb.2005.12.003\r\n\r\n16. Alon, U. (2007). Network motifs: theory and experimental approaches.\u00a0Nature reviews. Genetics,\u00a08(6), 450\u2013461. https://doi.org/10.1038/nrg2102\r\n\r\n17. Shoval, O., and Alon, U. (2010). SnapShot: network motifs.\u00a0Cell,\u00a0143(2), 326\u2013e1. https://doi.org/10.1016/j.cell.2010.09.050\r\n\r\n18. Mac\u00eda, J., Widder, S., and Sol\u00e9, R. (2009). Specialized or flexible feed-forward loop motifs: a question of topology.\u00a0BMC systems biology,\u00a03, 84. https://doi.org/10.1186/1752-0509-3-84\r\n\r\n19. Entus, R., Aufderheide, B., and Sauro, H.M. (2007). Design and implementation of three incoherent feed-forward motif based biological concentration sensors.\u00a0Systems and synthetic biology,\u00a01(3), 119\u2013128. https://doi.org/10.1007/s11693-007-9008-6\r\n\r\n20. Kaplan, S., Bren, A., Dekel, E., and Alon, U. (2008). The incoherent feed-forward loop can generate non-monotonic input functions for genes.\u00a0Molecular systems biology,\u00a04, 203. https://doi.org/10.1038/msb.2008.43\r\n\r\n21. Kim, D., Kwon, Y.K., and Cho, K.H. (2008). The biphasic behavior of incoherent feed-forward loops in biomolecular regulatory networks.\u00a0BioEssays : news and reviews in molecular, cellular and developmental biology,\u00a030(11-12), 1204\u20131211. https://doi.org/10.1002/bies.20839\r\n\r\n22. Goentoro, L., Shoval, O., Kirschner, M.W., and Alon, U. (2009). The incoherent feedforward loop can provide fold-change detection in gene regulation.\u00a0Molecular cell,\u00a036(5), 894\u2013899. https://doi.org/10.1016/j.molcel.2009.11.018\r\n\r\n23. Shoval, O., Goentoro, L., Hart, Y., Mayo, A., Sontag, E., and Alon, U. (2010). Fold-change detection and scalar symmetry of sensory input fields.\u00a0Proceedings of the National Academy of Sciences of the United States of America,\u00a0107(36), 15995\u201316000. https://doi.org/10.1073/pnas.1002352107\r\n\r\n\u202824. Hong, J., Brandt, N., Abdul-Rahman, F., Yang, A., Hughes, T., and Gresham, D. (2018). An incoherent feedforward loop facilitates adaptive tuning of gene expression.\u00a0eLife,\u00a07, e32323. https://doi.org/10.7554/eLife.32323\r\n\r\n\u202825. Hart, Y., and Alon, U. (2013). The utility of paradoxical components in biological circuits.\u00a0Molecular cell,\u00a049(2), 213\u2013221. https://doi.org/10.1016/j.molcel.2013.01.004\r\n\r\n26. Chalmers, A. (1982). What is This Thing Called Science? Open University Press. Introduction, xix.\r\n\r\n27. S\u00e9raphin, B., Kretzner, L., and Rosbash, M. (1988). A U1 snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5' cleavage site.\u00a0The EMBO journal,\u00a07(8), 2533\u20132538.\r\n\r\n28. Tsai, P.L., Zhao, C., Turner, E., and Schlieker, C. (2016). The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. eLife, 5, e16011. https://doi.org/10.7554/eLife.16011\r\n\r\n29. Chen, C.K., Blanco, M., Jackson, C., Aznauryan, E., Ollikainen, N., Surka, C., Chow, A., Cerase, A., McDonel, P., and Guttman, M. (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing.\u00a0Science (New York, N.Y.),\u00a0354(6311), 468\u2013472. https://doi.org/10.1126/science.aae0047\u2028\u202830. \r\n\r\n30. McHugh, C.A., Chen, C.K., Chow, A., Surka, C. F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M.J., Shishkin, A.A., Su, J., Lander, E.S., Hess, S., Plath, K., and Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.\u00a0Nature,\u00a0521(7551), 232\u2013236. https://doi.org/10.1038/nature14443\r\n\r\n31. Chu, C., Zhang, Q.C., da Rocha, S.T., Flynn, R.A., Bharadwaj, M., Calabrese, J.M., Magnuson, T., Heard, E., & Chang, H.Y. (2015). Systematic discovery of Xist RNA binding proteins.\u00a0Cell,\u00a0161(2), 404\u2013416. https://doi.org/10.1016/j.cell.2015.03.025\r\n\r\n32. Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T.B., and Brockdorff, N. (2015). A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.\u00a0Cell reports,\u00a012(4), 562\u2013572. https://doi.org/10.1016/j.celrep.2015.06.053\r\n\r\n33. Monfort, A., Di Minin, G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., and Wutz, A. (2015). Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.\u00a0Cell reports,\u00a012(4), 554\u2013561. https://doi.org/10.1016/j.celrep.2015.06.067\r\n\r\n\u202834. Shi, Y., Downes, M., Xie, W., Kao, H.Y., Ordentlich, P., Tsai, C.C., Hon, M., and Evans, R.M. (2001). Sharp, an inducible cofactor that integrates nuclear receptor repression and activation.\u00a0Genes & development,\u00a015(9), 1140\u20131151. https://doi.org/10.1101/gad.871201\r\n\r\n\u202835. Oswald, F., Kostezka, U., Astrahantseff, K., Bourteele, S., Dillinger, K., Zechner, U., Ludwig, L., Wilda, M., Hameister, H., Kn\u00f6chel, W., Liptay, S., and Schmid, R.M. (2002). SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway.\u00a0The EMBO journal,\u00a021(20), 5417\u20135426. https://doi.org/10.1093/emboj/cdf549\r\n\r\n36. Tsuji, M., Shinkura, R., Kuroda, K., Yabe, D., and Honjo, T. (2007). Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling. Proceedings of the National Academy of Sciences of the United States of America, 104(5), 1610\u20131615. https://doi.org/10.1073/pnas.0610520104\r\n\r\n37. Dossin, F., Pinheiro, I., \u017bylicz, J.J., Roensch, J., Collombet, S., Le Saux, A., Chelmicki, T., Attia, M., Kapoor, V., Zhan, Y., Dingli, F., Loew, D., Mercher, T., Dekker, J., and Heard, E. (2020). SPEN integrates transcriptional and epigenetic control of X-inactivation. Nature, 578(7795), 455\u2013460. https://doi.org/10.1038/s41586-020-1974-9\r\n\r\n38. Brown, C.J., and Willard, H.F. (1994). The human X-inactivation centre is not required for maintenance of X-chromosome inactivation.\u00a0Nature,\u00a0368(6467), 154\u2013156. https://doi.org/10.1038/368154a0\r\n\r\n39. Wutz, A., and Jaenisch, R. (2000). A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation.\u00a0Molecular cell,\u00a05(4), 695\u2013705. https://doi.org/10.1016/s1097-2765(00)80248-8\r\n\r\n40. Zhang, H., Zeitz, M.J., Wang, H., Niu, B., Ge, S., Li, W., Cui, J., Wang, G., Qian, G., Higgins, M.J., Fan, X., Hoffman, A.R., and Hu, J.F. (2014). Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus.\u00a0The Journal of cell biology,\u00a0204(1), 61\u201375. https://doi.org/10.1083/jcb.201304152\u2028\u202841. \r\n\r\n41. Bleris, L., Xie, Z., Glass, D., Adadey, A., Sontag, E., and Benenson, Y. (2011). Synthetic incoherent feedforward circuits show adaptation to the amount of their genetic template. Molecular systems biology,\u00a07, 519. https://doi.org/10.1038/msb.2011.49\r\n\r\n42. Ebert, M.S., and Sharp, P.A. (2012). Roles for microRNAs in conferring robustness to biological processes.\u00a0Cell,\u00a0149(3), 515\u2013524. https://doi.org/10.1016/j.cell.2012.04.005\r\n\r\n43. Elowitz, M.B., Levine, A.J., Siggia, E.D., and Swain, P.S. (2002). Stochastic gene expression in a single cell.\u00a0Science (New York, N.Y.),\u00a0297(5584), 1183\u20131186. https://doi.org/10.1126/science.1070919\r\n\r\n44. Blake, W.J., KAErn, M., Cantor, C.R., and Collins, J.J. (2003). Noise in eukaryotic gene expression.\u00a0Nature,\u00a0422(6932), 633\u2013637. https://doi.org/10.1038/nature01546\r\n\r\n45. Blake, W.J., Bal\u00e1zsi, G., Kohanski, M.A., Isaacs, F.J., Murphy, K.F., Kuang, Y., Cantor, C.R., Walt, D.R., and Collins, J.J. (2006). Phenotypic consequences of promoter-mediated transcriptional noise.\u00a0Molecular cell,\u00a024(6), 853\u2013865. https://doi.org/10.1016/j.molcel.2006.11.003\r\n\r\n46. Paulsson, J. (2004). Summing up the noise in gene networks.\u00a0Nature,\u00a0427(6973), 415\u2013418. https://doi.org/10.1038/nature02257\r\n\r\n47. Raser, J.M., and O'Shea, E.K. (2005). Noise in gene expression: origins, consequences, and control.\u00a0Science (New York, N.Y.),\u00a0309(5743), 2010\u20132013. https://doi.org/10.1126/science.1105891\r\n\r\n48. Newman, J.R., Ghaemmaghami, S., Ihmels, J., Breslow, D.K., Noble, M., DeRisi, J.L., and Weissman, J.S. (2006). Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise.\u00a0Nature,\u00a0441(7095), 840\u2013846. https://doi.org/10.1038/nature04785\r\n\r\n49. Sigal, A., Milo, R., Cohen, A., Geva-Zatorsky, N., Klein, Y., Liron, Y., Rosenfeld, N., Danon, T., Perzov, N., and Alon, U. (2006). Variability and memory of protein levels in human cells.\u00a0Nature,\u00a0444(7119), 643\u2013646. https://doi.org/10.1038/nature05316\r\n\r\n50. Osella, M., Bosia, C., Cor\u00e1, D., and Caselle, M. (2011). The role of incoherent microRNA-mediated feedforward loops in noise buffering.\u00a0PLoS computational biology,\u00a07(3), e1001101. https://doi.org/10.1371/journal.pcbi.1001101\r\n\r\n51. Li, X., Cassidy, J.J., Reinke, C.A., Fischboeck, S., and Carthew, R.W. (2009). A microRNA imparts robustness against environmental fluctuation during development.\u00a0Cell,\u00a0137(2), 273\u2013282. https://doi.org/10.1016/j.cell.2009.01.058\r\n\r\n52. Hornstein, E., and Shomron, N. (2006). Canalization of development by microRNAs.\u00a0Nature genetics,\u00a038 Suppl, S20\u2013S24. https://doi.org/10.1038/ng1803\r\n\r\n53. Quinodoz, S.A., Bhat, P., Ollikainen, N., Jachowicz, J., Banerjee, A.K., Chovanec, P., Blanco, M.R., Chow, A., Markaki, Y., Plath, K. and Guttman, M. (2020). RNA promotes the formation of spatial compartments in the nucleus. bioRxiv 2020.08.25.267435; https://doi.org/10.1101/2020.08.25.267435" ] }, "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "F30HL136080" } ] }, "collection": "CaltechTHESIS", "reviewer": "Melissa Ray", "local_group": { "items": [ "COVID-19" ] }, "deposited_by": "Abhik Banerjee", "deposited_on": "2021-02-12 23:30:46", "doi": "10.7907/tfb9-n887", "divisions": { "items": [ "div_bbe" ] }, "institution": "California Institute of Technology", "thesis_type": "phd", "thesis_advisor": { "items": [ { "email": "mguttman@caltech.edu", "id": "Guttman-M", "name": { "family": "Guttman", "given": "Mitchell" }, "orcid": "0000-0003-4748-9352", "role": "advisor" }, { "email": "evroth@its.caltech.edu", "id": "Rothenberg-E-V", "name": { "family": "Rothenberg", "given": "Ellen V." }, "orcid": "0000-0002-3901-347X", "role": "co-advisor" } ] }, "thesis_committee": { "items": [ { "email": "pws@caltech.edu", "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173", "role": "chair" }, { "email": "baltimo@caltech.edu", "id": "Baltimore-D-L", "name": { "family": "Baltimore", "given": "David L." }, "orcid": "0000-0001-8723-8190", "role": "member" }, { "email": "melowitz@caltech.edu", "id": "Elowitz-M-B", "name": { "family": "Elowitz", "given": "Michael B." }, "orcid": "0000-0002-1221-0967", "role": "member" }, { "email": "mguttman@caltech.edu", "id": "Guttman-M", "name": { "family": "Guttman", "given": "Mitchell" }, "orcid": "0000-0003-4748-9352", "role": "member" }, { "email": "evroth@its.caltech.edu", "id": "Rothenberg-E-V", "name": { "family": "Rothenberg", "given": "Ellen V." }, "orcid": "0000-0002-3901-347X", "role": "member" } ] }, "thesis_degree": "PHD", "thesis_degree_grantor": "California Institute of Technology", "thesis_defense_date": "2020-12-14", "gradofc_approval_date": "2021-02-12", "review_status": "approved", "option_major": { "items": [ "biology" ] }, "copyright_statement": "Author's Rights Authorization: I hereby certify that, if appropriate, I have obtained a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted here is the same as that approved by my advisory committee.\n\nI hereby grant to California Institute of Technology or its agents the non-exclusive license to archive and make accessible, under the conditions specified under \"Thesis Availability\" in this submission, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation, or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.", "pub_year": "2021", "author_list": "Banerjee, Abhik Kumar" } ]