Transcription-Austin最新文献

{"title":"Single-molecule insights into torsion and roadblocks in bacterial transcript elongation.","authors":"Jin Qian,&nbsp;Wenxuan Xu,&nbsp;David Dunlap,&nbsp;Laura Finzi","doi":"10.1080/21541264.2021.1997315","DOIUrl":"10.1080/21541264.2021.1997315","url":null,"abstract":"<p><p>During transcription, RNA polymerase (RNAP) translocates along the helical template DNA while maintaining high transcriptional fidelity. However, all genomes are dynamically twisted, writhed, and decorated by bound proteins and motor enzymes. In prokaryotes, proteins bound to DNA, specifically or not, frequently compact DNA into conformations that may silence genes by obstructing RNAP. Collision of RNAPs with these architectural proteins, may result in RNAP stalling and/or displacement of the protein roadblock. It is important to understand how rapidly transcribing RNAPs operate under different levels of supercoiling or in the presence of roadblocks. Given the broad range of asynchronous dynamics exhibited by transcriptional complexes, single-molecule assays, such as atomic force microscopy, fluorescence detection, optical and magnetic tweezers, etc. are well suited for detecting and quantifying activity with adequate spatial and temporal resolution. Here, we summarize current understanding of the effects of torsion and roadblocks on prokaryotic transcription, with a focus on single-molecule assays that provide real-time detection and readout.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"219-231"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632135/pdf/KTRN_12_1997315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39830211","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":"Nucleoid-associated proteins shape chromatin structure and transcriptional regulation across the bacterial kingdom.","authors":"Haley M Amemiya, Jeremy Schroeder, Peter L Freddolino","doi":"10.1080/21541264.2021.1973865","DOIUrl":"10.1080/21541264.2021.1973865","url":null,"abstract":"<p><p>Genome architecture has proven to be critical in determining gene regulation across almost all domains of life. While many of the key components and mechanisms of eukaryotic genome organization have been described, the interplay between bacterial DNA organization and gene regulation is only now being fully appreciated. An increasing pool of evidence has demonstrated that the bacterial chromosome can reasonably be thought of as chromatin, and that bacterial chromosomes contain transcriptionally silent and transcriptionally active regions analogous to heterochromatin and euchromatin, respectively. The roles played by histones in eukaryotic systems appear to be shared across a range of nucleoid-associated proteins (NAPs) in bacteria, which function to compact, structure, and regulate large portions of bacterial chromosomes. The broad range of extant NAPs, and the extent to which they differ from species to species, has raised additional challenges in identifying and characterizing their roles in all but a handful of model bacteria. Here we review the regulatory roles played by NAPs in several well-studied bacteria and use the resulting state of knowledge to provide a working definition for NAPs, based on their function, binding pattern, and expression levels. We present a screening procedure which can be applied to any species for which transcriptomic data are available. Finally, we note that NAPs tend to play two major regulatory roles - xenogeneic silencers and developmental regulators - and that many unrecognized potential NAPs exist in each bacterial species examined.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"182-218"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632127/pdf/KTRN_12_1973865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39398135","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":"Mfd - at the crossroads of bacterial DNA repair, transcriptional regulation and molecular evolvability.","authors":"Alexandra M Deaconescu","doi":"10.1080/21541264.2021.1982628","DOIUrl":"10.1080/21541264.2021.1982628","url":null,"abstract":"<p><p>For survival, bacteria need to continuously evolve and adapt to complex environments, including those that may impact the integrity of the DNA, the repository of genetic information to be passed on to future generations. The multiple factors of DNA repair share the substrate on which they operate with other key cellular machineries, principally those of replication and transcription, implying a high degree of coordination of DNA-based activities. In this review, I focus on progress made in the understanding of the protein factors operating at the crossroads of these three fundamental processes, with emphasis on the <i>mutation frequency decline</i> protein (Mfd, aka TRCF). Although Mfd research has a rich history that goes back in time for more than half a century, recent reports hint that much remains to be uncovered. I argue that besides being a transcription-repair coupling factor (TRCF), Mfd is also a global regulator of transcription and a pro-mutagenic factor, and that the way it interfaces with transcription, replication and nucleotide excision repair makes it an attractive candidate for the development of strategies to curb molecular evolution, hence, antibiotic resistance.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"156-170"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632110/pdf/KTRN_12_1982628.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39537604","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":"Rho-dependent transcription termination: a revisionist view.","authors":"Zhitai Hao,&nbsp;Vladimir Svetlov,&nbsp;Evgeny Nudler","doi":"10.1080/21541264.2021.1991773","DOIUrl":"https://doi.org/10.1080/21541264.2021.1991773","url":null,"abstract":"<p><p>Rho is a hexameric bacterial RNA helicase, which became a paradigm of factor-dependent transcription termination. The broadly accepted (\"textbook\") model posits a series of steps, wherein Rho first binds C-rich <i>Rho utilization</i> (<i>rut</i>) sites on nascent RNA, uses its ATP-dependent translocase activity to catch up with RNA polymerase (RNAP), and either pulls the transcript from the elongation complex or pushes RNAP forward, thus terminating transcription. However, this appealingly simple mechano-chemical model lacks a biological realism and is increasingly at odds with genetic and biochemical data. Here, we summarize recent structural and biochemical studies that have advanced our understanding of molecular details of RNA recognition, termination signaling, and RNAP inactivation in Rho-dependent transcription termination, rebalancing the view in favor of an alternative \"allosteric\" mechanism. In the revised model, Rho binds RNAP early in elongation assisted by the cofactors NusA and NusG, forming a pre-termination complex (PTC). The formation of PTC allows Rho to continuously sample nascent transcripts for a termination signal, which subsequently traps the elongation complex in an inactive state prior to its dissociation.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"171-181"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632121/pdf/KTRN_12_1991773.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39570205","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":"Transcription complexes as RNA chaperones.","authors":"Nelly Said,&nbsp;Markus C Wahl","doi":"10.1080/21541264.2021.1985931","DOIUrl":"https://doi.org/10.1080/21541264.2021.1985931","url":null,"abstract":"<p><p>To exert their functions, RNAs adopt diverse structures, ranging from simple secondary to complex tertiary and quaternary folds. <i>In vivo</i>, RNA folding starts with RNA transcription, and a wide variety of processes are coupled to co-transcriptional RNA folding events, including the regulation of fundamental transcription dynamics, gene regulation by mechanisms like attenuation, RNA processing or ribonucleoprotein particle formation. While co-transcriptional RNA folding and associated co-transcriptional processes are by now well accepted as pervasive regulatory principles in all organisms, investigations into the role of the transcription machinery in co-transcriptional folding processes have so far largely focused on effects of the order in which RNA regions are produced and of transcription kinetics. Recent structural and structure-guided functional analyses of bacterial transcription complexes increasingly point to an additional role of RNA polymerase and associated transcription factors in supporting co-transcriptional RNA folding by fostering or preventing strategic contacts to the nascent transcripts. In general, the results support the view that transcription complexes can act as RNA chaperones, a function that has been suggested over 30 years ago. Here, we discuss transcription complexes as RNA chaperones based on recent examples from bacterial transcription.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"126-155"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/f0/KTRN_12_1985931.PMC8632103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39830209","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":"Bacterial transcription during growth arrest.","authors":"Megan Bergkessel","doi":"10.1080/21541264.2021.1968761","DOIUrl":"10.1080/21541264.2021.1968761","url":null,"abstract":"<p><p>Bacteria in most natural environments spend substantial periods of time limited for essential nutrients and not actively dividing. While transcriptional activity under these conditions is substantially reduced compared to that occurring during active growth, observations from diverse organisms and experimental approaches have shown that new transcription still occurs and is important for survival. Much of our understanding of transcription regulation has come from measuring transcripts in exponentially growing cells, or from <i>in vitro</i> experiments focused on transcription from highly active promoters by the housekeeping RNA polymerase holoenzyme. The fact that transcription during growth arrest occurs at low levels and is highly heterogeneous has posed challenges for its study. However, new methods of measuring low levels of gene expression activity, even in single cells, offer exciting opportunities for directly investigating transcriptional activity and its regulation during growth arrest. Furthermore, much of the rich structural and biochemical data from decades of work on the bacterial transcriptional machinery is also relevant to growth arrest. In this review, the physiological changes likely affecting transcription during growth arrest are first considered. Next, possible adaptations to help facilitate ongoing transcription during growth arrest are discussed. Finally, new insights from several recently published datasets investigating mRNA transcripts in single bacterial cells at various growth phases will be explored. Keywords: Growth arrest, stationary phase, RNA polymerase, nucleoid condensation, population heterogeneity.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"232-249"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39390586","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":"Bacterial RNA synthesis: back to the limelight.","authors":"Irina Artsimovitch","doi":"10.1080/21541264.2021.2001236","DOIUrl":"https://doi.org/10.1080/21541264.2021.2001236","url":null,"abstract":"Bacterial RNA synthesis: back to the limelight Bacteria have been a mainstay of molecular biology, shaping our understanding of the fundamental principles of gene expression control for over half a century. The elegant simplicity of bacterial systems led to many textbook models. Early studies of transcription in bacteria and phages provided a foundation for analysis of more complex eukaryotic systems, and bacterial research started falling out of fashion, with its subjects increasingly seen as over-studied and far removed from modern public-health concerns. While bacterial systems are indeed simpler – from smaller, more information-packed genomes to fewer subunits in RNA polymerase (RNAP) – part of the simplicity in our explanatory models is due to experimental choices made by those who developed them. Limited by the tools and methods of earlier decades, researchers relied on elementary and direct approaches that nevertheless provided an evergreen source of insights that were generalized across the bacterial kingdom and beyond. However, bacteria live in complex environments and exchange not only metabolites but also genetic information. Studies of bacteria in exotic niches and extensive communities, from soils to shales to the human gut, prompted the development of new experimental and computational approaches, revealing that bacteria are very diverse, and many “bacterial” stereotypes do not apply to them all. In this Special Focus issue, we present a collection of reviews that reflect the rapidly changing field of bacterial transcription, highlighting the dawning realization that every aspect – the players, their parts, and their purpose in life and evolution – is more complex than we ever imagined. Key enzymes of the Central Dogma, RNAP and ribosome, are viewed as highly conserved machines. Yet, Miller et al. show that even the best-studied model bacteria, such as Bacillus subtilis and Escherichia coli, have notably diverse RNAPs [1]. Although biochemical and genetic data suggested that they used distinct strategies to regulate RNA synthesis, it took high-resolution cryo-EM structures to make it clear that even their enzymes are different, with two additional auxiliary subunits in B. subtilis “core” RNAP, ε and δ, thought to contribute to the transcription complex stability and disassembly, respectively [1]. Each RNAP has to adapt to the unique needs of its cell, and acquiring additional modules, either as large domain insertions in E. coli or as dissociable subunits, appears to be a common strategy; e.g., bacterial-type chloroplast RNAP apparently needs ten essential subunits to transcribe a ~150-kb genome. New approaches, such as cryo-electron tomography, can capture transcription complexes in their native environments and will no doubt show that bacteria use astonishingly diverse RNAPs and accessory factors. Coupling of transcription and translation is an accepted paradigm in prokaryotes that lack physical barriers between the two machinerie","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 4","pages":"89-91"},"PeriodicalIF":3.6,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632100/pdf/KTRN_12_2001236.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39737001","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":"CREB-mediated transcriptional activation of NRMT1 drives muscle differentiation.","authors":"John G Tooley, James P Catlin, Christine E Schaner Tooley","doi":"10.1080/21541264.2021.1963627","DOIUrl":"10.1080/21541264.2021.1963627","url":null,"abstract":"<p><p>The N-terminal methyltransferase NRMT1 is an important regulator of protein/DNA interactions and plays a role in many cellular processes, including mitosis, cell cycle progression, chromatin organization, DNA damage repair, and transcriptional regulation. Accordingly, loss of NRMT1 results in both developmental pathologies and oncogenic phenotypes. Though NRMT1 plays such important and diverse roles in the cell, little is known about its own regulation. To better understand the mechanisms governing NRMT1 expression, we first identified its predominant transcriptional start site and minimal promoter region with predicted transcription factor motifs. We then used a combination of luciferase and binding assays to confirm CREB1 as the major regulator of NRMT1 transcription. We tested which conditions known to activate CREB1 also activated NRMT1 transcription, and found CREB1-mediated NRMT1 expression was increased during recovery from serum starvation and muscle cell differentiation. To determine how NRMT1 expression affects myoblast differentiation, we used CRISPR/Cas9 technology to knock out NRMT1 expression in immortalized C2C12 mouse myoblasts. C2C12 cells depleted of NRMT1 lacked <i>Pax7</i> expression and were unable to proceed down the muscle differentiation pathway. Instead, they took on characteristics of C2C12 cells that have transdifferentiated into osteoblasts, including increased alkaline phosphatase and type I collagen expression and decreased proliferation. These data implicate NRMT1 as an important downstream target of CREB1 during muscle cell differentiation.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 2-3","pages":"72-88"},"PeriodicalIF":3.6,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555533/pdf/KTRN_12_1963627.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39319379","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":"Interplay between splicing and transcriptional pausing exerts genome-wide control over alternative polyadenylation.","authors":"Carmen Mora Gallardo,&nbsp;Ainhoa Sánchez de Diego,&nbsp;Carlos Martínez-A,&nbsp;Karel H M van Wely","doi":"10.1080/21541264.2021.1959244","DOIUrl":"https://doi.org/10.1080/21541264.2021.1959244","url":null,"abstract":"<p><p>Recent studies have identified multiple polyadenylation sites in nearly all mammalian genes. Although these are interpreted as evidence for alternative polyadenylation, our knowledge of the underlying mechanisms is still limited. Most studies only consider the immediate surroundings of gene ends, even though <i>in vitro</i> experiments have uncovered the involvement of external factors such as splicing. Whereas <i>in vivo</i> splicing manipulation was impracticable until recently, we now used mutants in the <i>Death Inducer Obliterator</i> (<i>DIDO</i>) gene to study their impact on 3' end processing. We observe multiple rounds of readthrough and gene fusions, suggesting that no arbitration between polyadenylation sites occurs. Instead, a window of opportunity seems to control end processing. Through the identification of T-rich sequence motifs, our data indicate that splicing and transcriptional pausing interact to regulate alternative polyadenylation. We propose that 3' splice site activation comprises a variable timer, which determines how long transcription proceeds before polyadenylation signals are recognized. Thus, the role of core polyadenylation signals could be more passive than commonly believed. Our results provide new insights into the mechanisms of alternative polyadenylation and expand the catalog of related aberrations.<b>Abbreviations</b> APA: alternative polyadenylation; bp: basepair; MEF: mouse embryonic fibroblasts; PA: polyadenylation; PAS: polyadenylation site; Pol II: (RNA) polymerase II ; RT-PCR:reverse-transcriptase PCR; SF:splicing factor; SFPQ:splicing factor rich in proline and glutamine; SS:splice site; TRSM:Thymidine rich sequence motif; UTR:untranslated terminal region.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 2-3","pages":"55-71"},"PeriodicalIF":3.6,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39299005","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":"Long noncoding RNAs: role and contribution in pancreatic cancer.","authors":"K T Ramya Devi,&nbsp;Dharshene Karthik,&nbsp;TharunSelvam Mahendran,&nbsp;M K Jaganathan,&nbsp;Sanjana Prakash Hemdev","doi":"10.1080/21541264.2021.1922071","DOIUrl":"https://doi.org/10.1080/21541264.2021.1922071","url":null,"abstract":"<p><p>Noncoding RNAs are proclaimed to be expressed in various cancer types and one such type is found to be pancreatic ductal adenocarcinoma (PDAC). The long noncoding RNAs (LncRNAs) affect the migration, invasion, and growth of tumor cells by playing important roles in the process of epigenesis, post-transcription, and transcriptional regulation along with the maintenance of apoptosis and cell cycle. It is quite subtle whether the alterations in lncRNAs would impact PDAC progression and development. This review throws a spotlight on the lncRNAs associated with tumor functions: MALAT-1, HOTAIR, HOXA13, H19, LINC01559, LINC00460, SNHG14, SNHG16, DLX6-AS1, MSC-AS1, ABHD11-AS1, DUXAP8, DANCR, XIST, DLEU2, etc. are upregulated lncRNAs whereas GAS5, HMlincRNA717, MIAT, LINC01111, lncRNA KCNK15-AS1, etc. are downregulated lncRNAs inhibiting the invasion and progression of PDAC. These data provided helps in the assessment of lncRNAs in the development, metastasis, and occurrence of PDAC and also play a vital role in the evolution of biomarkers and therapeutic agents for the treatment of PDAC.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"12 1","pages":"12-27"},"PeriodicalIF":3.6,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2021.1922071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39033187","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}