Transcription-Austin最新文献

{"title":"Recent molecular insights into canonical pre-mRNA 3'-end processing.","authors":"Yadong Sun,&nbsp;Keith Hamilton,&nbsp;Liang Tong","doi":"10.1080/21541264.2020.1777047","DOIUrl":"https://doi.org/10.1080/21541264.2020.1777047","url":null,"abstract":"<p><p>The majority of eukaryotic messenger RNA precursors (pre-mRNAs) undergo cleavage and polyadenylation at their 3' end. This canonical 3'-end processing depends on sequence elements in the pre-mRNA as well as a mega-dalton protein machinery. The cleavage site in mammalian pre-mRNAs is located between an upstream poly(A) signal, most frequently an AAUAAA hexamer, and a GU-rich downstream sequence element. This review will summarize recent advances from the studies on this canonical 3'-end processing machinery. They have revealed the molecular mechanism for the recognition of the poly(A) signal and provided the first glimpse into the overall architecture of the machinery. The studies also show that the machinery is highly dynamic conformationally, and extensive re-arrangements are necessary for its activation. Inhibitors targeting the active site of the CPSF73 nuclease of this machinery have anti-cancer, anti-inflammatory and anti-protozoal effects, indicating that CPSF73 and pre-mRNA 3'-end processing in general are attractive targets for drug discovery.</p><p><strong>Abbreviations: </strong>APA: alternative polyadenylation; β-CASP: metallo-β-lactamase-associated CPSF Artemis SNM1/PSO2; CTD: C-terminal domain; CF: cleavage factor; CPF: cleavage and polyadenylation factor; CPSF: cleavage and polyadenylation specificity factor; CstF: cleavage stimulation factor; DSE: downstream element; HAT: half a TPR; HCC: histone pre-mRNA cleavage complex; mCF: mammalian cleavage factor; mPSF: mammalian polyadenylation specificity factor; mRNA: messenger RNA; nt: nucleotide; NTD: N-terminal domain; PAP: polyadenylate polymerase; PAS: polyadenylation signal; PIM: mPSF interaction motif; Poly(A): polyadenylation, polyadenylate; Pol II: RNA polymerase II; pre-mRNA: messenger RNA precursor; RRM: RNA recognition module, RNA recognition motif; snRNP: small nuclear ribonucleoprotein; TPR: tetratricopeptide repeat; UTR: untranslated region; ZF: zinc finger.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 2","pages":"83-96"},"PeriodicalIF":3.6,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2020.1777047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38034642","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":"Lessons from eRNAs: understanding transcriptional regulation through the lens of nascent RNAs.","authors":"Joseph F Cardiello,&nbsp;Gilson J Sanchez,&nbsp;Mary A Allen,&nbsp;Robin D Dowell","doi":"10.1080/21541264.2019.1704128","DOIUrl":"https://doi.org/10.1080/21541264.2019.1704128","url":null,"abstract":"<p><p>Nascent transcription assays, such as global run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), have uncovered a myriad of unstable RNAs being actively produced from numerous sites genome-wide. These transcripts provide a more complete and immediate picture of the impact of regulatory events. Transcription factors recruit RNA polymerase II, effectively initiating the process of transcription; repressors inhibit polymerase recruitment. Efficiency of recruitment is dictated by sequence elements in and around the RNA polymerase loading zone. A combination of sequence elements and RNA binding proteins subsequently influence the ultimate stability of the resulting transcript. Some of these transcripts are capable of providing feedback on the process, influencing subsequent transcription. By monitoring RNA polymerase activity, nascent assays provide insights into every step of the regulated process of transcription.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"3-18"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1704128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37473781","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 control by enhancers: working remotely for improved performance.","authors":"Joaquin M Espinosa","doi":"10.1080/21541264.2020.1724673","DOIUrl":"https://doi.org/10.1080/21541264.2020.1724673","url":null,"abstract":"Completion of the Human Genome Project almost twenty years ago produced a humbling surprise: biological complexity is driven not so much by the number of genes in a genome, but rather by increased regulatory diversity. The ability of multicellular organisms to turn genes on and off in various combinations not only drives the appearance of a cornucopia of differentiated cell types with vastly different functions, but also provides the capacity for homeostasis in a wide range of environmental conditions. Central to this increased regulatory capacity are DNA sequences that control gene activity. Among these, distal enhancer elements have captured the imagination of scientists since their initial discovery in 1983 [1–3], and their study continues to produce new mysteries. How do enhancers really work? How much of their action is driven by the mere binding of transcription factors? What are the roles of chromatin modifications and three-dimensional conformation in enhancer function? How about enhancer-derived RNAs (eRNAs)? Finding answers to these questions is not simply a basic science exercise, as genetic alterations leading to enhancer dysfunction, such as translocations, single nucleotide polymorphisms, and mutations are recognized sources of human variation, susceptibility to disease, and known drivers of cancer progression. Within this framework, in this issue of Transcription, we are glad to publish a series of reviews focused on enhancers. First, Lewis et al. get us started with a thorough and entertaining update on transcriptional control by enhancers and eRNAs[4]. Then, Cardiello et al. dive deeper into the fascinating world of eRNAs and other RNA species arising from regulatory elements identified by novel measurements of nascent RNA[5]. We then transition into the realm of chromatin, where Rahnamoun et al. report on the regulatory interplay between eRNAs, histone modifications, and epigenetic readers[6]. Next, Yao et al. provide an updated account of the role of enhancer reprogramming in tumorigenesis and cancer development[7]. Lastly, BarajasMora and Feeney discuss recent interesting results about the role of enhancers as organizers of chromatin configurations important for shaping the repertoire of immunoglobulins produced by VDJ recombination[8]. Altogether, this collection of reviews provides an important update on the state of the field, while also identifying new avenues of future research. We are grateful to all authors for their expert contributions, and hope that the readers of Transcription will treasure this issue focused on enhancers.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"1-2"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2020.1724673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37640431","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":"The role of enhancer RNAs in epigenetic regulation of gene expression.","authors":"Homa Rahnamoun,&nbsp;Paola Orozco,&nbsp;Shannon M Lauberth","doi":"10.1080/21541264.2019.1698934","DOIUrl":"https://doi.org/10.1080/21541264.2019.1698934","url":null,"abstract":"<p><p>Since the discovery that enhancers can support transcription, the roles of enhancer RNAs have remained largely elusive. We identified that enhancer RNAs interact with and augment bromodomain engagement with acetylated chromatin. Here, we discuss our recent findings and the potential mechanisms underlying the regulation and functions of enhancer RNA-bromodomain associations.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"19-25"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1698934","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37446102","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":"Enhancers as regulators of antigen receptor loci three-dimensional chromatin structure.","authors":"E Mauricio Barajas-Mora,&nbsp;Ann J Feeney","doi":"10.1080/21541264.2019.1699383","DOIUrl":"https://doi.org/10.1080/21541264.2019.1699383","url":null,"abstract":"<p><p>Enhancers are defined as regulatory elements that control transcription in a cell-type and developmental stage-specific manner. They achieve this by physically interacting with their cognate gene promoters. Significantly, these interactions can occur through long genomic distances since enhancers may not be near their cognate promoters. The optimal coordination of enhancer-regulated transcription is essential for the function and identity of the cell. Although great efforts to fully understand the principles of this type of regulation are ongoing, other potential functions of the long-range chromatin interactions (LRCIs) involving enhancers are largely unexplored. We recently uncovered a new role for enhancer elements in determining the three-dimensional (3D) structure of the immunoglobulin kappa (Igκ) light chain receptor locus suggesting a structural function for these DNA elements. This enhancer-mediated locus configuration shapes the resulting Igκ repertoire. We also propose a role for enhancers as critical components of sub-topologically associating domain (subTAD) formation and nuclear spatial localization.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"37-51"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2019.1699383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37451360","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":"Correction.","authors":"","doi":"10.1080/21541264.2020.1726602","DOIUrl":"https://doi.org/10.1080/21541264.2020.1726602","url":null,"abstract":"","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"52"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2020.1726602","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37640432","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":"Epigenetic plasticity of enhancers in cancer.","authors":"Jie Yao,&nbsp;Ji Chen,&nbsp;Lian-Yun Li,&nbsp;Min Wu","doi":"10.1080/21541264.2020.1713682","DOIUrl":"https://doi.org/10.1080/21541264.2020.1713682","url":null,"abstract":"<p><p>Enhancers are cis-acting elements with many sites bound by transcription factors and activate transcription over long distance. Histone modifications are critical for enhancer activity and utilized as hallmarks for the identification of putative enhancers. Monomethylation of histone H3 lysine 4 (H3K4me1) is the mark for enhancer priming; acetylation of histone H3 lysine 27 (H3K27ac) for active enhancers and trimethylation of histone H3 lysine 27 (H3K27me3) for silent enhancers. Recent studies from multiple groups have provided evidence that enhancer reprogramming, especially gain of enhancer activity, is closely related to tumorigenesis and cancer development. In this review, we will summarize the recent discoveries about enhancer regulation and the mechanisms of enhancer reprogramming in tumorigenesis, and discuss the potential application of enhancer manipulation in precision medicine.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"11 1","pages":"26-36"},"PeriodicalIF":3.6,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541264.2020.1713682","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37547505","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":"Change in inorganic phosphate physical state can regulate transcription","authors":"M. Gottesman, A. Mustaev","doi":"10.1080/21541264.2019.1682454","DOIUrl":"https://doi.org/10.1080/21541264.2019.1682454","url":null,"abstract":"ABSTRACT Inorganic phosphate (Pi), a ubiquitous metabolite, is involved in all major biochemical pathways. We demonstrate that, in vitro, MgHPO4 (the intracellular Pi form) at physiological concentrations can exist in a metastable supersaturated dissolved state or as a precipitate. We have shown that in solution, MgHPO4 strongly stimulates exonuclease nascent transcript cleavage by RNA polymerase. We report here that MgHPO4 precipitate selectively and efficiently inhibits transcription initiation in vitro. In view of the MgHPO4 solubility and in vitro sensitivity of RNA synthesis to MgHPO4 precipitate, at physiological concentrations, MgHPO4 should cause a 50–98% inhibition of cellular RNA synthesis, thus exerting a strong regulatory action. The effects of Pi on transcription in vivo will, therefore, reflect the physical state of intracellular Pi.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"104 1","pages":"187 - 194"},"PeriodicalIF":3.6,"publicationDate":"2019-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80672770","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":"Evidence that dissociation of Spt16 from transcribed genes is partially dependent on RNA Polymerase II termination","authors":"Jessica B Campbell, M. Edwards, Sydney A Ozersky, Andrea A Duina","doi":"10.1080/21541264.2019.1685837","DOIUrl":"https://doi.org/10.1080/21541264.2019.1685837","url":null,"abstract":"ABSTRACT FACT (FAcilitates Chromatin Transactions) is a highly conserved histone chaperone complex in eukaryotic cells that can interact and manipulate nucleosomes in order to promote a variety of DNA-based processes and to maintain the integrity of chromatin throughout the genome. Whereas key features of the physical interactions that occur between FACT and nucleosomes in vitro have been elucidated in recent years, less is known regarding FACT functional dynamics in vivo. Using the Saccharomyces cerevisiae system, we now provide evidence that at least at some genes dissociation of the FACT subunit Spt16 from their 3′ ends is partially dependent on RNA Polymerase II (Pol II) termination. Combined with other studies, our results are consistent with a two-phase mechanism for FACT dissociation from genes, one that occurs upstream from Pol II dissociation and is Pol II termination-independent and the other that occurs further downstream and is dependent on Pol II termination.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"21 1","pages":"195 - 206"},"PeriodicalIF":3.6,"publicationDate":"2019-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85065934","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":"Clock-controlled rhythmic transcription: is the clock enough and how does it work?","authors":"Joshua R Beytebiere, Ben J Greenwell, A. Sahasrabudhe, J. Menet","doi":"10.1080/21541264.2019.1673636","DOIUrl":"https://doi.org/10.1080/21541264.2019.1673636","url":null,"abstract":"ABSTRACT Circadian clocks regulate the rhythmic expression of thousands of genes underlying the daily oscillations of biological functions. Here, we discuss recent findings showing that circadian clock rhythmic transcriptional outputs rely on additional mechanisms than just clock gene DNA binding, which may ultimately contribute to the plasticity of circadian transcriptional programs.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":"20 1","pages":"212 - 221"},"PeriodicalIF":3.6,"publicationDate":"2019-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81989959","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}