Cold Spring Harbor symposia on quantitative biology最新文献

{"title":"A Conversation with David Bartel.","authors":"","doi":"10.1101/sqb.2019.84.039313","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039313","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"259-261"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37479824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation with Phillip Sharp.","authors":"","doi":"10.1101/sqb.2019.84.039487","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039487","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"291-293"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37572661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation with Igor Ulitsky.","authors":"","doi":"10.1101/sqb.2019.84.039529","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039529","url":null,"abstract":"Dr. Ulitsky: I first became interested in noncoding RNAs towards the end of my PhD studies. We were looking at regulatory networks governing transcriptional regulation for protein-coding genes. Then we got interested in microRNAs, so I went for my postdoc to Dave Bartel’s lab at the Whitehead Institute. This was around the same time that people began doing large-scale maps and seeing that there is a lot of transcription outside the boundaries of proteincoding genes producing RNAs that seemed to be very similar to mRNAs, but it wasn’t clear whether these were functional or what they might be doing. Together with another postdoc in the lab, Alena Shkumatava, we became interested in studying to what extent long noncoding RNAs are found in different species. We compared zebrafish and human and mouse and we found that there is a lot of turnover, but there is a subset of lncRNAs that is deeply conserved. They’re found throughout vertebrates and we could show that two of them were actually functionally important in development of zebrafish and that this functionality was conserved. When I started my own lab about 6 years ago, we decided to focus on understanding what kind of things these long noncoding RNAs are doing and how they’re carrying out these functions.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"296-298"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039529","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37587762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Coactivator PGC-1α Binding to Newly Synthesized RNA via CBP80: A Nexus for Co- and Posttranscriptional Gene Regulation.","authors":"Xavier Rambout,&nbsp;Hana Cho,&nbsp;Lynne E Maquat","doi":"10.1101/sqb.2019.84.040212","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.040212","url":null,"abstract":"<p><p>Mammalian cells have many quality-control mechanisms that regulate protein-coding gene expression to ensure proper transcript synthesis, processing, and translation. Should a step in transcript metabolism fail to fulfill requisite spatial, temporal, or structural criteria, including the proper acquisition of RNA-binding proteins, then that step will halt, fail to proceed to the next step, and ultimately result in transcript degradation. Quality-control mechanisms constitute a continuum of processes that initiate in the nucleus and extend to the cytoplasm. Here, we present published and unpublished data for protein-coding genes whose expression is activated by the transcriptional coactivator PGC-1α. We show that PGC-1α movement from chromatin, to which it is recruited by DNA-binding proteins, to CBP80 at the 5' cap of nascent transcripts begins a series of co- and posttranscriptional quality- and quantity-control steps that, in total, ensure proper gene expression.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"47-54"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37838502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nuclear RNA Degradation Pathway Helps Silence Polycomb/H3K27me3-Marked Loci in <i>Caenorhabditis elegans</i>.","authors":"Anna Mattout,&nbsp;Dimos Gaidatzis,&nbsp;Véronique Kalck,&nbsp;Susan M Gasser","doi":"10.1101/sqb.2019.84.040238","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.040238","url":null,"abstract":"<p><p>In fission yeast and plants, RNA-processing pathways contribute to heterochromatin silencing, complementing well-characterized pathways of transcriptional repression. However, it was unclear whether this additional level of regulation occurs in metazoans. In a genetic screen, we uncovered a pathway of silencing in <i>Caenorhabditis elegans</i> somatic cells, whereby the highly conserved, RNA-binding complex LSM2-8 contributes to the repression of heterochromatic reporters and endogenous genes bearing the Polycomb mark H3K27me3. Importantly, the LSM2-8 complex works cooperatively with a 5'-3' exoribonuclease, XRN-2, and disruption of the pathway leads to selective mRNA stabilization. LSM2-8 complex-mediated RNA degradation does not target nor depend on H3K9me2/me3, unlike previously described pathways of heterochromatic RNA degradation. Up-regulation of <i>lsm-8</i>-sensitive loci coincides with a localized drop in H3K27me3 levels in the <i>lsm-8</i> mutant. Put into the context of epigenetic control of gene expression, it appears that targeted RNA degradation helps repress a subset of H3K27me3-marked genes, revealing an unappreciated layer of regulation for facultative heterochromatin in animals.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"141-153"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37885099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstitution of siRNA Biogenesis In Vitro: Novel Reaction Mechanisms and RNA Channeling in the RNA-Directed DNA Methylation Pathway.","authors":"Jasleen Singh,&nbsp;Craig S Pikaard","doi":"10.1101/sqb.2019.84.039842","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039842","url":null,"abstract":"<p><p>Eukaryotes deploy RNA-mediated gene silencing pathways to guard their genomes against selfish genetic elements, such as transposable elements and invading viruses. In plants, RNA-directed DNA methylation (RdDM) is used to silence selfish elements at the level of transcription. This process involves 24-nt short interfering RNAs (siRNAs) and longer noncoding RNAs to which the siRNAs base-pair. Recently, we showed that 24-nt siRNA biogenesis could be recapitulated in the test tube using purified enzymes, yielding biochemical answers to numerous questions left unresolved by prior genetic and genomic studies. Interestingly, each enzyme has activities that program what happens in the next step, thus channeling the RNAs within the RdDM pathway and restricting their diversion into alternative pathways. However, a similar mechanistic understanding is lacking for other important steps of the RdDM pathway. We discuss some of the steps most in need of biochemical investigation and important questions still in need of answers.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"195-201"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37885174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation with Oliver Rando.","authors":"","doi":"10.1101/sqb.2019.84.039651","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039651","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"288-290"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37735329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation with Karla Neugebauer.","authors":"","doi":"10.1101/sqb.2019.84.039636","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039636","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"282-284"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37750890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Noncoding RNAs in Development and Regeneration of the Neural Lineage.","authors":"Hadas Hezroni,&nbsp;Rotem Ben Tov Perry,&nbsp;Igor Ulitsky","doi":"10.1101/sqb.2019.84.039347","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039347","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs) are gathering increasing attention toward their roles in different biological systems. In mammals, the richest repertoires of lncRNAs are expressed in the brain and in the testis, and the diversity of lncRNAs in the nervous system is thought to be related to the diversity and the complexity of its cell types. Supporting this notion, many lncRNAs are differentially expressed between different regions of the brain or in particular cell types, and many lncRNAs are dynamically expressed during embryonic or postnatal neurogenesis. Less is known about the functions of these genes, if any, but they are increasingly implicated in diverse processes in health and disease. Here, we review the current knowledge about the roles and importance of lncRNAs in the central and peripheral nervous systems and discuss the specific niches within gene regulatory networks that might be preferentially occupied by lncRNAs.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"165-177"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37511824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conversation with Susan Gasser.","authors":"","doi":"10.1101/sqb.2019.84.039214","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039214","url":null,"abstract":"Dr. Gasser: We’ve been studying the mechanisms of heterochromatin repression, of different ways to keep genes silent. Most of that is at the level of transcription through the formation of heterochromatin, but in a screen for derepression of heterochromatin we found three subunits of an RNA-controlling complex. All the other hits in this screen were chromatin modulators as we expected, so these three were a surprise. This was in C. elegans, but this complex is conserved from bacteria to yeast to humans. It’s called the LSM complex for “like Sm” proteins. We read up on the LSm complex, and found that it comes in two forms. There’s one in the cytoplasm and another in the nucleus. They share six subunits, but the seventh, either subunit 1 or 8, is specific for either cytoplasm or nucleus. The first thing we showed was that the role in silencing was through the nuclear complex. That was good, because it meant that it was probably working at the level of genes. We then looked at the proteins that are supposedly interacting with this nuclear complex. Its normal role is to bind U6 RNA, catalyze or chaperone splicing, and then help trigger the degradation of the spliced-out intron, through an RNA exonuclease called XRN2. XRN2, but not U6 RNA, was also involved in the heterochromatic silencing of our reporter. Then we asked, “Which endogenous genes are sensitive to this RNA degradation mode of silencing?”We detected several hundred genes that were derepressed—or up-regulated—in the absence of this LSM complex or of XRN2. We asked, “What’s the nature of these genes?” First, we saw that they were all very poorly expressed in wild-type worms. Second, we checked their chromatin state by monitoring enrichment of histone marks, and we found that 95% carried histone H3K27me3, the characteristic methylation deposited by Polycomb. Polycomb is known to silence genes. It’s usually thought to create facultative heterochromatin in a tissueor cell type–specific manner. It actually poises genes in an “off” state, but such that they can also be switched “on,” depending on differentiation. It’s quite intriguing that all the genes that were controlled by this LSM2–8 were Polycomb-marked facultative heterochromatin. So we were faced with the question, “How does it work?” Polycomb normally represses by transcriptional repression, by blocking transcription, but here we were looking at RNA degradation. We checked specific genes that were sensitive to this RNA-degrading complex and showed that if you mutate the LSM8 subunit, which is specific for the XRN2-binding nuclear complex, then you stabilize a low level of transcripts from such target genes. Apparently, although genes are repressed by Polycomb, there’s a low level of promiscuous transcription possible. Then we asked if the same genes are regulated by XRN2, LSM8, and Polycomb. And indeed, they overlap significantly. Finally, we asked the question, “Does RNA degradation feed back in any way to the Polycomb mark?” Does the ","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"266-267"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37511826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}