Pub Date : 2020-02-27DOI: 10.1101/sqb.2019.84.039784
Deirdre C Tatomer, Jeremy E Wilusz
{"title":"Erratum: Attenuation of Eukaryotic Protein-Coding Gene Expression via Premature Transcription Termination.","authors":"Deirdre C Tatomer, Jeremy E Wilusz","doi":"10.1101/sqb.2019.84.039784","DOIUrl":"10.1101/sqb.2019.84.039784","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37685792","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}
Pub Date : 2019-07-01DOI: 10.1101/sqb.2018.83.038828
Kristen Delevich, A Wren Thomas, Linda Wilbrecht
{"title":"Corrigendum: Adolescence and \"Late Blooming\" Synapses of the Prefrontal Cortex.","authors":"Kristen Delevich, A Wren Thomas, Linda Wilbrecht","doi":"10.1101/sqb.2018.83.038828","DOIUrl":"10.1101/sqb.2018.83.038828","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37381399","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}
Pub Date : 2019-01-01Epub Date: 2020-06-01DOI: 10.1101/sqb.2019.84.040352
Furqan M Fazal, Howard Y Chang
RNAs are trafficked and localized with exquisite precision inside the cell. Studies of candidate messenger RNAs have shown the vital importance of RNA subcellular location in development and cellular function. New sequencing- and imaging-based methods are providing complementary insights into subcellular localization of RNAs transcriptome-wide. APEX-seq and ribosome profiling as well as proximity-labeling approaches have revealed thousands of transcript isoforms are localized to distinct cytotopic locations, including locations that defy biochemical fractionation and hence were missed by prior studies. Sequences in the 3' and 5' untranslated regions (UTRs) serve as "zip codes" to direct transcripts to particular locales, and it is clear that intronic and retrotransposable sequences within transcripts have been co-opted by cells to control localization. Molecular motors, nuclear-to-cytosol RNA export, liquid-liquid phase separation, RNA modifications, and RNA structure dynamically shape the subcellular transcriptome. Location-based RNA regulation continues to pose new mysteries for the field, yet promises to reveal insights into fundamental cell biology and disease mechanisms.
{"title":"Subcellular Spatial Transcriptomes: Emerging Frontier for Understanding Gene Regulation.","authors":"Furqan M Fazal, Howard Y Chang","doi":"10.1101/sqb.2019.84.040352","DOIUrl":"10.1101/sqb.2019.84.040352","url":null,"abstract":"<p><p>RNAs are trafficked and localized with exquisite precision inside the cell. Studies of candidate messenger RNAs have shown the vital importance of RNA subcellular location in development and cellular function. New sequencing- and imaging-based methods are providing complementary insights into subcellular localization of RNAs transcriptome-wide. APEX-seq and ribosome profiling as well as proximity-labeling approaches have revealed thousands of transcript isoforms are localized to distinct cytotopic locations, including locations that defy biochemical fractionation and hence were missed by prior studies. Sequences in the 3' and 5' untranslated regions (UTRs) serve as \"zip codes\" to direct transcripts to particular locales, and it is clear that intronic and retrotransposable sequences within transcripts have been co-opted by cells to control localization. Molecular motors, nuclear-to-cytosol RNA export, liquid-liquid phase separation, RNA modifications, and RNA structure dynamically shape the subcellular transcriptome. Location-based RNA regulation continues to pose new mysteries for the field, yet promises to reveal insights into fundamental cell biology and disease mechanisms.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"31-45"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37999989","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}
Pub Date : 2019-01-01Epub Date: 2020-02-04DOI: 10.1101/sqb.2019.84.039495
Run-Wen Yao, Chu-Xiao Liu, Ling-Ling Chen
RNA processing is critical for eukaryotic mRNA maturation and function. It appears there is no exception for other types of RNAs. Long noncoding RNAs (lncRNAs) represent a subclass of noncoding RNAs, have sizes of >200 nucleotides (nt), and participate in various aspects of gene regulation. Although many lncRNAs are capped, polyadenylated, and spliced just like mRNAs, others are derived from primary transcripts of RNA polymerase II and stabilized by forming circular structures or by ending with small nucleolar RNA-protein complexes. Here we summarize the recent progress in linking the processing and function of these unconventionally processed lncRNAs; we also discuss how directional RNA movement is achieved using the radial flux movement of nascent precursor ribosomal RNA (pre-rRNA) in the human nucleolus as an example.
{"title":"Linking RNA Processing and Function.","authors":"Run-Wen Yao, Chu-Xiao Liu, Ling-Ling Chen","doi":"10.1101/sqb.2019.84.039495","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039495","url":null,"abstract":"<p><p>RNA processing is critical for eukaryotic mRNA maturation and function. It appears there is no exception for other types of RNAs. Long noncoding RNAs (lncRNAs) represent a subclass of noncoding RNAs, have sizes of >200 nucleotides (nt), and participate in various aspects of gene regulation. Although many lncRNAs are capped, polyadenylated, and spliced just like mRNAs, others are derived from primary transcripts of RNA polymerase II and stabilized by forming circular structures or by ending with small nucleolar RNA-protein complexes. Here we summarize the recent progress in linking the processing and function of these unconventionally processed lncRNAs; we also discuss how directional RNA movement is achieved using the radial flux movement of nascent precursor ribosomal RNA (pre-rRNA) in the human nucleolus as an example.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"67-82"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37611726","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}
Pub Date : 2019-01-01Epub Date: 2020-06-09DOI: 10.1101/sqb.2019.84.040394
Jean-Sébastien Parent, Filipe Borges, Atsushi Shimada, Robert A Martienssen
Small RNA molecules can target a particular virus, gene, or transposable element (TE) with a high degree of specificity. Their ability to move from cell to cell and recognize targets in trans also allows building networks capable of regulating a large number of related targets at once. In the case of epigenetic silencing, small RNA may use the widespread distribution of TEs in eukaryotic genomes to coordinate many loci across developmental and generational time. Here, we discuss the intriguing role of plant small RNA in targeting transposons and repeats in pollen and seeds. Epigenetic reprogramming in the germline and early seed development provides a mechanism to control genome dosage, imprinted gene expression, and incompatible hybridizations via the "triploid block."
{"title":"Small RNA Function in Plants: From Chromatin to the Next Generation.","authors":"Jean-Sébastien Parent, Filipe Borges, Atsushi Shimada, Robert A Martienssen","doi":"10.1101/sqb.2019.84.040394","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.040394","url":null,"abstract":"<p><p>Small RNA molecules can target a particular virus, gene, or transposable element (TE) with a high degree of specificity. Their ability to move from cell to cell and recognize targets in <i>trans</i> also allows building networks capable of regulating a large number of related targets at once. In the case of epigenetic silencing, small RNA may use the widespread distribution of TEs in eukaryotic genomes to coordinate many loci across developmental and generational time. Here, we discuss the intriguing role of plant small RNA in targeting transposons and repeats in pollen and seeds. Epigenetic reprogramming in the germline and early seed development provides a mechanism to control genome dosage, imprinted gene expression, and incompatible hybridizations via the \"triploid block.\"</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"133-140"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.040394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38030631","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}
Pub Date : 2019-01-01Epub Date: 2020-02-18DOI: 10.1101/sqb.2019.84.039560
Dr. Zhang: Our work looks at the diversity of CRISPR systems. CRISPR is not a single system; there are many different types. This new system is something where a transposable element called Tn7 has, over the course of evolution, co-opted a CRISPR so that it can use the RNA targeting mechanism of CRISPR to spread itself to viruses or plasmids. By studying the molecular mechanism of this, we realized that it’s a potentially programmable way to be able to introduce DNA into the genome. One of the major hurdles of gene editing is we can cut DNA, but introducing DNA into the genome in a precise way has been challenging. Using these transposable elements that are RNA-guided, there’s the potential to develop a new genome-editing tool.
{"title":"A Conversation with Feng Zhang.","authors":"","doi":"10.1101/sqb.2019.84.039560","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039560","url":null,"abstract":"Dr. Zhang: Our work looks at the diversity of CRISPR systems. CRISPR is not a single system; there are many different types. This new system is something where a transposable element called Tn7 has, over the course of evolution, co-opted a CRISPR so that it can use the RNA targeting mechanism of CRISPR to spread itself to viruses or plasmids. By studying the molecular mechanism of this, we realized that it’s a potentially programmable way to be able to introduce DNA into the genome. One of the major hurdles of gene editing is we can cut DNA, but introducing DNA into the genome in a precise way has been challenging. Using these transposable elements that are RNA-guided, there’s the potential to develop a new genome-editing tool.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"302-304"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039560","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37654808","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}
Pub Date : 2019-01-01Epub Date: 2020-02-18DOI: 10.1101/sqb.2019.84.039388
{"title":"A Conversation with Leemor Joshua-Tor.","authors":"","doi":"10.1101/sqb.2019.84.039388","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039388","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"271-273"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37654809","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}
Pub Date : 2019-01-01Epub Date: 2019-12-20DOI: 10.1101/sqb.2019.84.038992
{"title":"A Conversation with Andrés Aguilera.","authors":"","doi":"10.1101/sqb.2019.84.038992","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.038992","url":null,"abstract":"","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"256-258"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37479828","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}
Pub Date : 2019-01-01Epub Date: 2020-01-23DOI: 10.1101/sqb.2019.84.039412
Dr. Maquat: In human diseases of the type that we studied, translation of an mRNA terminates prematurely. The disease-associated mutation is either a frameshift or a nonsense mutation that generates a premature termination codon, which, when recognized by a ribosome, triggers decay of the mRNA. This is a good thing in the sense that if a cell were to make truncated proteins, these proteins could be toxic. The open reading frame of the mutated mRNA is abnormally short, and therefore the encoded protein would be truncated, with the potential to gum up the cellular machine it works in. We figured out the rules for how a cell differentiates a normal termination codon, which generally doesn’t trigger mRNA decay, from a premature termination codon, which generally does.
{"title":"A Conversation with Lynne Maquat.","authors":"","doi":"10.1101/sqb.2019.84.039412","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039412","url":null,"abstract":"Dr. Maquat: In human diseases of the type that we studied, translation of an mRNA terminates prematurely. The disease-associated mutation is either a frameshift or a nonsense mutation that generates a premature termination codon, which, when recognized by a ribosome, triggers decay of the mRNA. This is a good thing in the sense that if a cell were to make truncated proteins, these proteins could be toxic. The open reading frame of the mutated mRNA is abnormally short, and therefore the encoded protein would be truncated, with the potential to gum up the cellular machine it works in. We figured out the rules for how a cell differentiates a normal termination codon, which generally doesn’t trigger mRNA decay, from a premature termination codon, which generally does.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"279-281"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37572663","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}
Pub Date : 2019-01-01Epub Date: 2020-03-18DOI: 10.1101/sqb.2019.84.039420
Dr. Jaffrey: I’m going to talk about our work on RNA modifications and, in particular, methylated adenosine. Most of the mRNA [messenger RNA] in the cell is composed of A, C, G, and U, but a tiny bit—maybe one in every 300–400 adenosines—is methylated, and when it’s methylated on the nitrogen of adenosine, it’s called mA. We normally don’t think of mRNA as containing that many modifications; we think of tRNA [transfer RNA] and other RNAs as having modifications. This was discovered way back in 1974 when scientists were beginning to understand how mRNA capping and other phenomena occur. When they were doing metabolic labeling to study the mG cap on mRNA, they ended up inadvertently discovering that there were actually methyl modifications inside mRNA, and with some clever biochemistry they figured out it was mA. The people who did this were Dawn Kelley and Robert Perry at Fox Chase and Fritz Rottman and other researchers like Jim Darnell. Some of the pioneers of molecular biology were involved in discovering this modification. mAwas known to be low abundance, but even though it was discovered way back then, almost nothing has been known since about what its function could be. It’s very appealing to think that it might be a modification like phosphorylation is for proteins. The potential that mA has some sort of regulatory function has been overlooked, and it’s for many reasons. First, some people didn’t even think that mA was really in mRNA, because when you purify mRNAyou actually have a lot of contaminants and they thought maybe mA could have been from tRNA or ribosomal RNA. But people like Jim Darnell did experiments where he did exceptionally high-purity purification, at least to the ability that they had at the time, and they still were able to see mA. So, there was belief—but still controversy—about whether it was really in mRNA. The other thing is, how do you study mA? mA behaves exactly like adenosine when you do reverse transcription. If you take mRNA and you make cDNA [complementary DNA], which is the reverse transcription step in molecular biology, you’re going to lose any methyl marks that were there. A lot of people abandoned the field and quickly moved into splicing because that was discovered in the end of the ’70s. A lot of this was lost and it wasn’t even in textbooks, but there were a few researchers who stayed on it. Fritz Rottman at CaseWestern was really the pioneer who cloned the enzyme. It’s called METTL3, or methyltransferase-like enzyme 3. Then, as with so many other things in molecular biology the breakthroughs came from yeast and plants. Some scientists knocked out the enzyme in yeast and they found a very remarkable sporulation defect. In plants they found seeds would go to one stage of development and stop. That was Rupert Fray’s paper in 2008. When we saw that paper we were just completely shocked; we never even heard of this modification. I had a postdoc who started shortly thereafter; her name is Kate Meyer and she’
{"title":"A Conversation with Samie Jaffrey.","authors":"","doi":"10.1101/sqb.2019.84.039420","DOIUrl":"https://doi.org/10.1101/sqb.2019.84.039420","url":null,"abstract":"Dr. Jaffrey: I’m going to talk about our work on RNA modifications and, in particular, methylated adenosine. Most of the mRNA [messenger RNA] in the cell is composed of A, C, G, and U, but a tiny bit—maybe one in every 300–400 adenosines—is methylated, and when it’s methylated on the nitrogen of adenosine, it’s called mA. We normally don’t think of mRNA as containing that many modifications; we think of tRNA [transfer RNA] and other RNAs as having modifications. This was discovered way back in 1974 when scientists were beginning to understand how mRNA capping and other phenomena occur. When they were doing metabolic labeling to study the mG cap on mRNA, they ended up inadvertently discovering that there were actually methyl modifications inside mRNA, and with some clever biochemistry they figured out it was mA. The people who did this were Dawn Kelley and Robert Perry at Fox Chase and Fritz Rottman and other researchers like Jim Darnell. Some of the pioneers of molecular biology were involved in discovering this modification. mAwas known to be low abundance, but even though it was discovered way back then, almost nothing has been known since about what its function could be. It’s very appealing to think that it might be a modification like phosphorylation is for proteins. The potential that mA has some sort of regulatory function has been overlooked, and it’s for many reasons. First, some people didn’t even think that mA was really in mRNA, because when you purify mRNAyou actually have a lot of contaminants and they thought maybe mA could have been from tRNA or ribosomal RNA. But people like Jim Darnell did experiments where he did exceptionally high-purity purification, at least to the ability that they had at the time, and they still were able to see mA. So, there was belief—but still controversy—about whether it was really in mRNA. The other thing is, how do you study mA? mA behaves exactly like adenosine when you do reverse transcription. If you take mRNA and you make cDNA [complementary DNA], which is the reverse transcription step in molecular biology, you’re going to lose any methyl marks that were there. A lot of people abandoned the field and quickly moved into splicing because that was discovered in the end of the ’70s. A lot of this was lost and it wasn’t even in textbooks, but there were a few researchers who stayed on it. Fritz Rottman at CaseWestern was really the pioneer who cloned the enzyme. It’s called METTL3, or methyltransferase-like enzyme 3. Then, as with so many other things in molecular biology the breakthroughs came from yeast and plants. Some scientists knocked out the enzyme in yeast and they found a very remarkable sporulation defect. In plants they found seeds would go to one stage of development and stop. That was Rupert Fray’s paper in 2008. When we saw that paper we were just completely shocked; we never even heard of this modification. I had a postdoc who started shortly thereafter; her name is Kate Meyer and she’","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"84 ","pages":"268-270"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2019.84.039420","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37750889","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}
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