Transcription-Austin最新文献

{"title":"New means to an end: mRNA export activity impacts alternative polyadenylation","authors":"Jihae Shin, Hong Cheng, B. Tian","doi":"10.1080/21541264.2019.1658557","DOIUrl":"https://doi.org/10.1080/21541264.2019.1658557","url":null,"abstract":"ABSTRACT Gene expression involves multiple co- and post-transcriptional processes that have been increasingly found intertwined. A recent work by our groups (Chen et al. Mol Cell, 2019) indicates that expression of alternative polyadenylation isoforms in mammalian cells can be controlled by nuclear export activities. This regulation has distinct impacts on genes having different sizes and nucleotide contents, and involves RNA polymerase II distribution toward the 3ʹ end of genes. This work raises a number of intriguing questions concerning how 3ʹ end processing and nuclear export are integrated and how their regulation feeds back to transcription.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"300 1","pages":"207 - 211"},"PeriodicalIF":3.6,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73590160","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":"Exploiting phage strategies to modulate bacterial transcription.","authors":"Markus C Wahl,&nbsp;Ranjan Sen","doi":"10.1080/21541264.2019.1684137","DOIUrl":"https://doi.org/10.1080/21541264.2019.1684137","url":null,"abstract":"<p><p>Bacteriophages employ small proteins to usurp host molecular machinery, thereby interfering with central metabolic processes in infected bacteria. Generally, phages inhibit or redirect host transcription to favor transcription of their own genomes. Mechanistic and structural studies of phage-modulated host transcription may provide inspirations for the development of novel antibacterial substances.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"222-230"},"PeriodicalIF":3.6,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1684137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40552370","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":"Identify gene expression pattern change at transcriptional and post-transcriptional levels.","authors":"Ji-Gang Zhang,&nbsp;Chao Xu,&nbsp;Lan Zhang,&nbsp;Wei Zhu,&nbsp;Hui Shen,&nbsp;Hong-Wen Deng","doi":"10.1080/21541264.2019.1575159","DOIUrl":"https://doi.org/10.1080/21541264.2019.1575159","url":null,"abstract":"<p><p>Gene transcription is regulated with distinct sets of regulatory factors at multiple levels. Transcriptional and post-transcriptional regulation constitute two major regulation modes of gene expression to either activate or repress the initiation of transcription and thereby control the number of proteins synthesized during translation. Disruptions of the proper regulation patterns at transcriptional and post-transcriptional levels are increasingly recognized as causes of human diseases. Consequently, identifying the differential gene expression at transcriptional and post-transcriptional levels respectively is vital to identify potential disease-associated and/or causal genes and understand their roles in the disease development. Here, we proposed a novel method with a linear mixed model that can identify a set of differentially expressed genes at transcriptional and post-transcriptional levels. The simulation and real data analysis showed our method could provide an accurate way to identify genes subject to aberrant transcriptional and post-transcriptional regulation and reveal the potential causal genes that contributed to the diseases.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 3","pages":"137-146"},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1575159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36910378","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":"Balanced between order and disorder: a new phase in transcription elongation control and beyond.","authors":"Huasong Lu,&nbsp;Rongdiao Liu,&nbsp;Qiang Zhou","doi":"10.1080/21541264.2019.1570812","DOIUrl":"https://doi.org/10.1080/21541264.2019.1570812","url":null,"abstract":"<p><p>We recently reported that the cyclin T1 histidine-rich domain creates a phase-separated environment to promote hyperphosphorylation of RNA polymerase II C-terminal domain and robust transcriptional elongation by P-TEFb. Here, we discuss this and several other recent discoveries to demonstrate that phase separation is important for controlling various aspects of transcription.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 3","pages":"157-163"},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1570812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36870818","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":"Transcribe this way: Rap1 confers promoter directionality by repressing divergent transcription.","authors":"Andrew C K Wu, Folkert J Van Werven","doi":"10.1080/21541264.2019.1608716","DOIUrl":"10.1080/21541264.2019.1608716","url":null,"abstract":"<p><p>In eukaryotes, divergent transcription is a major source of noncoding RNAs. Recent studies have uncovered that in yeast, the transcription factor Rap1 restricts transcription in the divergent direction and thereby controls promoter directionality. Here, we summarize these findings, propose regulatory principles, and discuss the implications for eukaryotic gene regulation.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 3","pages":"164-170"},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37376592","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":"PML-RARα induces all-trans retinoic acid-dependent transcriptional activation through interaction with MED1.","authors":"Tomoya Fukuoka,&nbsp;Asami Kawai,&nbsp;Taku Takahara,&nbsp;Mahiro Mori,&nbsp;Robert G Roeder,&nbsp;Natsumi Hasegawa,&nbsp;Mitsuhiro Ito","doi":"10.1080/21541264.2019.1624467","DOIUrl":"https://doi.org/10.1080/21541264.2019.1624467","url":null,"abstract":"<p><p>Transcriptional activation by PML-RARα, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). However, the mechanism by which the liganded PML-RARα complex leads to the formation of the preinitiation complex has been unidentified. Here we demonstrate that the Mediator subunit MED1 plays an important role in the ATRA-dependent activation of the PML-RARα-bound promoter. Luciferase reporter assays showed that PML-RARα induced significant transcription at pharmacological doses (1 μM) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RARα at physiological doses (1 nM) of ATRA. Transcription depended upon the interaction of PML-RARα with the two LxxLL nuclear receptor recognition motifs of MED1, and LxxLL→LxxAA mutations led to minimal transcription. Mechanistically, MED1 interacted ATRA-dependently with the RARα portion of PML-RARα through the two LxxLL motifs of MED1. These results suggest that PML-RARα initiates ATRA-induced transcription through its interaction with MED1.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 3","pages":"147-156"},"PeriodicalIF":3.6,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1624467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37278822","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":"Transcriptional CDKs in the spotlight.","authors":"Joaquin M Espinosa","doi":"10.1080/21541264.2019.1597479","DOIUrl":"https://doi.org/10.1080/21541264.2019.1597479","url":null,"abstract":"At every active gene in any genome, there is a transcription cycle, defined as the collective set of biochemical reactions that control RNA polymerase activity, from promoter binding to polymerase recycling. The transcription cycle serves as a command center where multiple sources of information are integrated to ensure that RNA synthesis across genomic loci is tailored precisely to the needs of the cell and organism. Despite its critical importance, our understanding of the transcription cycle is limited, and this lack of knowledge hampers our ability to manipulate transcriptional activity for myriad purposes, both in basic research and the applied sciences. Within this framework, in this issue of Transcription, we are excited to publish a series of reviews focused on key regulators of the transcription cycle: the transcriptional cyclindependent kinases or tCDKs. CDKs are a distinct class of serine-threonine protein kinases that share a core set of features, including the requirement of a cyclin partner and phosphorylation of their ‘activating T-loops’ by a CDK-activating kinase (CAK). In vertebrates, a distinct set of CDKs have clear roles in the regulation of cell cycle progression (CDK1, −2, −4, −6), while a different subset is involved mostly in transcriptional control (tCDKs: CDK7, −8, −9, −12, −13, −19) (ref 1–3). Our understanding of tCDKs has evolved rapidly in the last decade, yet for some of these proteins, our knowledge is still minimal, as in the cases of CDK12, CDK13, and CDK19. Even for the more well-studied tCDKs, such as CDK7 and CDK9, recent discoveries have changed our view of their mechanism of action and their roles in cell biology. Thus, we felt at Transcription that the time was right to have an updated view of the field, with a focus on recent discoveries and future venues for research. The need for these reviews is further justified by the increasing recognition that tCDKs could be valid targets of pharmacological intervention for the management of a number of human pathologies. In this issue of Transcription, Robert Fisher gets us started with an entertaining and thorough update on the state of affairs for CDK7, arguably the most multifaceted of the tCDKs, describing unanticipated roles for this enzyme in capping, termination, and polymerase recycling, while also sharing promising news about the therapeutic value of CDK7 inhibitors [4]. Then, Bacon and D’Orso bring us up to speed on CDK9, which they accurately describe as a “signaling hub” for transcriptional control, providing detailed descriptions of the mechanisms regulating CDK9 activity, as well as the roles of CDK9 in gene and enhancer transcription, RNA processing, chromatin regulation, and its roles in human disease [5]. Next, Fant and Taatjes provide an expert testimony about the Mediator-associated kinases, CDK8 and CDK19, introducing new and intriguing roles in enhancer-promoter communication, transcriptional memory, metabolism, and, in the case of CDK19, kina","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 2","pages":"45-46"},"PeriodicalIF":3.6,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1597479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37120021","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":"Regulatory functions of the Mediator kinases CDK8 and CDK19.","authors":"Charli B Fant,&nbsp;Dylan J Taatjes","doi":"10.1080/21541264.2018.1556915","DOIUrl":"https://doi.org/10.1080/21541264.2018.1556915","url":null,"abstract":"<p><p>The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC and MED12, which activate CDK8/CDK19 kinase function, and MED13, which enables their association with the Mediator complex. The Mediator kinases affect RNA polymerase II (pol II) transcription indirectly, through phosphorylation of transcription factors and by controlling Mediator structure and function. In this review, we discuss cellular roles of the Mediator kinases and mechanisms that enable their biological functions. We focus on sequence-specific, DNA-binding transcription factors and other Mediator kinase substrates, and how CDK8 or CDK19 may enable metabolic and transcriptional reprogramming through enhancers and chromatin looping. We also summarize Mediator kinase inhibitors and their therapeutic potential. Throughout, we note conserved and divergent functions between yeast and mammalian CDK8, and highlight many aspects of kinase module function that remain enigmatic, ranging from potential roles in pol II promoter-proximal pausing to liquid-liquid phase separation.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 2","pages":"76-90"},"PeriodicalIF":3.6,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2018.1556915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36813218","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":"Roles of CDKs in RNA polymerase II transcription of the HIV-1 genome.","authors":"Andrew P Rice","doi":"10.1080/21541264.2018.1542254","DOIUrl":"https://doi.org/10.1080/21541264.2018.1542254","url":null,"abstract":"<p><p>Studies of RNA Polymerase II (Pol II) transcription of the HIV-1 genome are of clinical interest, as the insight gained may lead to strategies to selectively reactivate latent viruses in patients in whom viral replication is suppressed by antiviral drugs. Such a targeted reactivation may contribute to a functional cure of infection. This review discusses five Cyclin-dependent kinases - CDK7, CDK9, CDK11, CDK2, and CDK8 - involved in transcription and processing of HIV-1 RNA. CDK7 is required for Pol II promoter clearance of reactivated viruses; CDK7 also functions as an activating kinase for CDK9 when resting CD4⁺ T cells harboring latent HIV-1 are activated. CDK9 is targeted by the viral Tat protein and is essential for productive Pol II elongation of the HIV-1 genome. CDK11 is associated with the TREX/THOC complex and it functions in the 3' end processing and polyadenylation of HIV-1 transcripts. CDK2 phosphorylates Tat and CDK9 and this stimulates Tat activation of Pol II transcription. CDK8 may stimulate Pol II transcription of the HIV-1 genome through co-recruitment with NF-κB to the viral promoter. Some notable open questions are discussed concerning the roles of these CDKs in HIV-1 replication and viral latency.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 2","pages":"111-117"},"PeriodicalIF":3.6,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2018.1542254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36675028","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":"Cdk7: a kinase at the core of transcription and in the crosshairs of cancer drug discovery.","authors":"Robert P Fisher","doi":"10.1080/21541264.2018.1553483","DOIUrl":"10.1080/21541264.2018.1553483","url":null,"abstract":"<p><p>The transcription cycle of RNA polymerase II (Pol II) is regulated by a set of cyclin-dependent kinases (CDKs). Cdk7, associated with the transcription initiation factor TFIIH, is both an effector CDK that phosphorylates Pol II and other targets within the transcriptional machinery, and a CDK-activating kinase (CAK) for at least one other essential CDK involved in transcription. Recent studies have illuminated Cdk7 functions that are executed throughout the Pol II transcription cycle, from promoter clearance and promoter-proximal pausing, to co-transcriptional chromatin modification in gene bodies, to mRNA 3´-end formation and termination. Cdk7 has also emerged as a target of small-molecule inhibitors that show promise in the treatment of cancer and inflammation. The challenges now are to identify the relevant targets of Cdk7 at each step of the transcription cycle, and to understand how heightened dependence on an essential CDK emerges in cancer, and might be exploited therapeutically.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"10 2","pages":"47-56"},"PeriodicalIF":3.6,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602562/pdf/ktrn-10-02-1553483.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36716578","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}