{"title":"A Conversation with Caroline Dean.","authors":"","doi":"10.1101/sqb.2019.84.039024","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039024","url":null,"abstract":"Dr. Dean: My lab works on how plants know when to flower, so I got into this wonderful world of chromatin and RNA through quite an unintentional route. Many years ago I went back to the U.K., having been a postdoc in the U.S., and decided seasonal timing was really interesting. The place I live in—Norwich—has fairly distinct winters and in spring we have this wonderful bloom. The question is, how is flowering so synchronized? My lab decided to study the molecular control of flowering, focusing on how plants decide whether to overwinter before flowering, and how they perceive winter. The many genetic routes we used to study these questions led us into the study of one gene. It’s a gene that encodes a repressor of flowering. To be able to flower, the plant switches that gene off through a cold-induced Polycomb switching mechanism. As we dissected this mechanism, we came across a set of antisense transcripts at the repressor locus so we have spent time dissecting how regulatory RNAs affect the chromatin environment of the locus, which affects the transcriptional output, which then affects whether the plants actually need winter and whether they can respond to winter.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"264-265"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37479827","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 Jeremy Wilusz.","authors":"","doi":"10.1101/sqb.2019.84.039511","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039511","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"299-301"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039511","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37587761","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}
Sarah R Hansen, Adedeji M Aderounmu, Helen M Donelick, Brenda L Bass
{"title":"Dicer's Helicase Domain: A Meeting Place for Regulatory Proteins.","authors":"Sarah R Hansen, Adedeji M Aderounmu, Helen M Donelick, Brenda L Bass","doi":"10.1101/sqb.2019.84.039750","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039750","url":null,"abstract":"<p><p>The function of Dicer's helicase domain has been enigmatic since its discovery. Why do only some Dicers require ATP, despite a high degree of sequence conservation in their helicase domains? We discuss evolutionary considerations based on differences between vertebrate and invertebrate antiviral defense, and how the helicase domain has been co-opted in extant organisms as the binding site for accessory proteins. Many accessory proteins are double-stranded RNA binding proteins, and we propose models for how they modulate Dicer function and catalysis.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"185-193"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37743349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dorcas Cummings Lecture.","authors":"","doi":"10.1101/sqb.2019.84.040139","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.040139","url":null,"abstract":"Dr. Jennifer Doudna presented the Dorcas Cummings lecture entitled “Editing the Code of Life: The Future of Genome Editing” to friends and neighbors of Cold Spring Harbor Laboratory and Symposium participants on Saturday, June 1, 2019. Dr. Doudna holds the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and is a Professor in the Departments of Molecular & Cell Biology and of Chemistry at the University of California, Berkeley, and the Executive Director of the Innovative Genomics Institute.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"245-250"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.040139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37999985","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}
Paulina Pawlica, Jessica Sheu-Gruttadauria, Ian J MacRae, Joan A Steitz
{"title":"How Complementary Targets Expose the microRNA 3' End for Tailing and Trimming during Target-Directed microRNA Degradation.","authors":"Paulina Pawlica, Jessica Sheu-Gruttadauria, Ian J MacRae, Joan A Steitz","doi":"10.1101/sqb.2019.84.039321","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039321","url":null,"abstract":"<p><p>microRNAs (miRNAs) are crucial for posttranscriptional regulation of messenger RNAs. \"Classical\" miRNA targets predominantly interact with the miRNA seed sequence located near the miRNA 5' end. Interestingly, certain transcripts that exhibit extensive complementarity to the miRNAs 3' region, instead of being subjected to regulation, induce miRNA decay in a process termed target-directed miRNA degradation (TDMD). Here, we review recent advances in understanding the molecular mechanisms of TDMD. Specifically, we discuss how extensive miRNA complementarity to TDMD-inducing targets results in displacement of the miRNA 3' end from its protective pocket in the Argonaute protein. Unprotected miRNA 3' ends are then available for enzymatic attack by still-unidentified cellular enzymes. Identification of these cellular enzymes and discovery of additional TDMD-inducing transcripts are subjects for future research.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"179-183"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37611728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeetayu Biswas, Leti Nunez, Sulagna Das, Young J Yoon, Carolina Eliscovich, Robert H Singer
{"title":"Zipcode Binding Protein 1 (ZBP1; IGF2BP1): A Model for Sequence-Specific RNA Regulation.","authors":"Jeetayu Biswas, Leti Nunez, Sulagna Das, Young J Yoon, Carolina Eliscovich, Robert H Singer","doi":"10.1101/sqb.2019.84.039396","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039396","url":null,"abstract":"<p><p>The fate of an RNA, from its localization, translation, and ultimate decay, is dictated by interactions with RNA binding proteins (RBPs). β-actin mRNA has functioned as the classic example of RNA localization in eukaryotic cells. Studies of β-actin mRNA over the past three decades have allowed understanding of how RBPs, such as ZBP1 (IGF2BP1), can control both RNA localization and translational status. Here, we summarize studies of β-actin mRNA and focus on how ZBP1 serves as a model for understanding interactions between RNA and their binding protein(s). Central to the study of RNA and RBPs were technological developments that occurred along the way. We conclude with a future outlook highlighting new technologies that may be used to address still unanswered questions about RBP-mediated regulation of mRNA during its life cycle, within the cell.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37667005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Conversation with Alberto Kornblihtt.","authors":"","doi":"10.1101/sqb.2019.84.039354","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039354","url":null,"abstract":"Dr. Kornblihtt: I work on alternative splicing and the coupling with transcription and chromatin, but in partic-ular on recent unpublished results that we obtained in the system of the SMN2 [survival of motor neurons 2] gene in terms of enhancing exon 7 inclusion in the therapy of spinal muscular atrophy [SMA]. My lab has been working for more than 20 years on the coupling between transcription and splicing, focusing mainly on kinetic coupling. We found that slow elongation can increase inclusion of certain exons in the mature mRNA [messen-ger RNA]. More recently, we also found that slow elongation can produce skipping of certain exons. Among the exons that are sensitive to elongation, ∼ 80% respond to the first rule — slow elongation increases inclusion — and 20% respond to the second mode in which slow elongation promotes skipping. This is because it gives more time for inhibitors of exon inclusion to bind to the pre-mRNA.Inthecase of exon 7 of spinal muscular atrophy, humans have two genes. When SMN1 is mutated, SMN2 , which is the backup gene, cannot cope with the lack of SMN protein because it has several mutations that make exon 7 poorly included into the mature mRNA. Adrian Krainer has developed a new drug called Spinraza that is an oligonucleotide that is able to displace the negative factors from the pre-mRNA and allow exon 7 to be more included. This is fantastic, and it has success in every of SMA. we found that exon 7 inclusion also to elongation in the second mode,","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"274-275"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039354","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37479823","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 Karen Adelman.","authors":"","doi":"10.1101/sqb.2019.84.039008","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039008","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"253-255"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37479826","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 Maria-Elena Torres-Padilla.","authors":"","doi":"10.1101/sqb.2019.84.039578","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039578","url":null,"abstract":"Dr. Torres-Padilla: We are interested in understanding how these very early cells of the very early embryo are actually able to establish andmaintain the largest plasticity that one can think of. It’s quite remarkable. Everybody, at some point, was a single cell. The question is how that single cell is able to generate a new being: not only all the tissues and cells that we have in our body, but really how that single cell builds up the whole program that we call “totipotency.” The system is difficult in that we have very limited materials. Obviously, we don’t do experiments with humans, but we do use the mouse and other species as a model to understand these transitions. But you don’t get a lot of embryos to try to understand biochemically what happens with stem cells and so on. The system is really fascinating, but it is a challenge.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"294-295"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37654810","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":"Functional and Mechanistic Interplay of Host and Viral Alternative Splicing Regulation during Influenza Infection.","authors":"Matthew G Thompson, Kristen W Lynch","doi":"10.1101/sqb.2019.84.039040","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039040","url":null,"abstract":"<p><p>Alternative splicing is a pervasive gene regulatory mechanism utilized by both mammalian cells and viruses to expand their genomic coding capacity. The process of splicing and the RNA sequences that guide this process are the same in mammalian and viral transcripts; however, viruses lack the splicing machinery and therefore must usurp both the host spliceosome and many of the associated regulatory proteins in order to correctly process their genes. Here, we use the example of the influenza A virus to both describe how viruses utilize host splicing factors to regulate their own splicing and provide examples of how viral infection can, in turn, alter host splicing. Importantly, we show that at least some of the viral-induced changes in host splicing occur in genes that alter the efficiency of influenza replication. We emphasize the importance of increased understanding of the mechanistic interplay between host and viral splicing, and its functional consequences, in uncovering potential antiviral vulnerabilities.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"123-131"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38187627","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}