Journal of Molecular Biology最新文献

Context-Dependent and Locus-Specific Role of H3K36 Methylation in Transcriptional Regulation. H3K36 甲基化在转录调控中的上下文依赖性和基因座特异性作用

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-09-19 DOI: 10.1016/j.jmb.2024.168796

Min Kyung Lee, Na Hyun Park, Soo Young Lee, TaeSoo Kim

{"title":"Context-Dependent and Locus-Specific Role of H3K36 Methylation in Transcriptional Regulation.","authors":"Min Kyung Lee, Na Hyun Park, Soo Young Lee, TaeSoo Kim","doi":"10.1016/j.jmb.2024.168796","DOIUrl":"10.1016/j.jmb.2024.168796","url":null,"abstract":"H3K36 methylation is a critical histone modification involved in transcription regulation. It involves the mono (H3K36me1), di (H3K36me2), and/or tri-methylation (H3K36me3) of lysine 36 on histone H3 by methyltransferases. In yeast, Set2 catalyzes all three methylation states. By contrast, in higher eukaryotes, at least eight methyltransferases catalyze different methylation states, including SETD2 for H3K36me3 and the NSD family for H3K36me2 in vivo. Both Set2 and SETD2 interact with the phosphorylated CTD of RNA Pol II, which links H3K36 methylation to transcription. In yeast, H3K36me3 and H3K36me2 peak at the 3' ends of genes. In higher eukaryotes, this is also true for H3K36me3 but not for H3K36me2, which is enriched at the 5' ends of genes and intergenic regions, suggesting that H3K36me2 and H3K36me3 may play different regulatory roles. Whether H3K36me1 demonstrates preferential distribution remains unclear. H3K36me3 is essential for inhibiting transcription elongation. It also suppresses cryptic transcription by promoting histone deacetylation by the histone deacetylases Rpd3S (yeast) and variant NuRD (higher eukaryotes). H3K36me3 also facilitates DNA methylation by DNMT3B, thereby preventing spurious transcription initiation. H3K36me3 not only represses transcription since it promotes the activation of mRNA and cryptic promoters in response to environmental changes by targeting the histone acetyltransferase NuA3 in yeast. Further research is needed to elucidate the methylation state- and locus-specific functions of H3K36me1 and the mechanisms that regulate it.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168796"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII. CDK9-SPT5 轴控制 RNAPII 的转录延伸。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-08-13 DOI: 10.1016/j.jmb.2024.168746

Rui Sun, Robert P Fisher

{"title":"The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII.","authors":"Rui Sun, Robert P Fisher","doi":"10.1016/j.jmb.2024.168746","DOIUrl":"10.1016/j.jmb.2024.168746","url":null,"abstract":"The RNA polymerase II (RNAPII) transcription cycle is regulated at every stage by a network of cyclin-dependent protein kinases (CDKs) and protein phosphatases. Progression of RNAPII from initiation to termination is marked by changing patterns of phosphorylation on the highly repetitive carboxy-terminal domain (CTD) of RPB1, its largest subunit, suggesting the existence of a CTD code. In parallel, the conserved transcription elongation factor SPT5, large subunit of the DRB sensitivity-inducing factor (DSIF), undergoes spatiotemporally regulated changes in phosphorylation state that may be directly linked to the transitions between transcription-cycle phases. Here we review insights gained from recent structural, biochemical, and genetic analyses of human SPT5, which suggest that two of its phosphorylated regions perform distinct functions at different points in transcription. Phosphorylation within a flexible, RNA-binding linker promotes release from the promoter-proximal pause-frequently a rate-limiting step in gene expression-whereas modifications in a repetitive carboxy-terminal region are thought to favor processive elongation, and are removed just prior to termination. Phosphorylations in both motifs depend on CDK9, catalytic subunit of positive transcription elongation factor b (P-TEFb); their different timing of accumulation on chromatin and function during the transcription cycle might reflect their removal by different phosphatases, different kinetics of phosphorylation by CDK9, or both. Perturbations of SPT5 regulation have profound impacts on viability and development in model organisms through largely unknown mechanisms, while enzymes that modify SPT5 have emerged as potential therapeutic targets in cancer; elucidating a putative SPT5 code is therefore a high priority.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168746"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NusG-Spt5 Transcription Factors: Universal, Dynamic Modulators of Gene Expression. NusG-Spt5 转录因子：基因表达的通用动态调节因子

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-10-05 DOI: 10.1016/j.jmb.2024.168814

Rachel A Mooney, Junqiao Zhu, Jason Saba, Robert Landick

{"title":"NusG-Spt5 Transcription Factors: Universal, Dynamic Modulators of Gene Expression.","authors":"Rachel A Mooney, Junqiao Zhu, Jason Saba, Robert Landick","doi":"10.1016/j.jmb.2024.168814","DOIUrl":"10.1016/j.jmb.2024.168814","url":null,"abstract":"The accurate and efficient biogenesis of RNA by cellular RNA polymerase (RNAP) requires accessory factors that regulate the initiation, elongation, and termination of transcription. Of the many discovered to date, the elongation regulator NusG-Spt5 is the only universally conserved transcription factor. With orthologs and paralogs found in all three domains of life, this ubiquity underscores their ancient and essential regulatory functions. NusG-Spt5 proteins evolved to maintain a similar binding interface to RNAP through contacts of the NusG N-terminal domain (NGN) that bridge the main DNA-binding cleft. We propose that varying strength of these contacts, modulated by tethering interactions, either decrease transcriptional pausing by smoothing the rugged thermodynamic landscape of transcript elongation or enhance pausing, depending on which conformation of RNAP is stabilized by NGN contacts. NusG-Spt5 contains one (in bacteria and archaea) or more (in eukaryotes) C-terminal domains that use a KOW fold to contact diverse targets, tether the NGN, and control RNA biogenesis. Recent work highlights these diverse functions in different organisms. Some bacteria contain multiple specialized NusG paralogs that regulate subsets of operons via sequence-specific targeting, controlling production of antibiotics, toxins, or capsule proteins. Despite their common origin, NusG orthologs can differ in their target selection, interacting partners, and effects on RNA synthesis. We describe the current understanding of NusG-Spt5 structure, interactions with RNAP and other regulators, and cellular functions including significant recent progress from genome-wide analyses, single-molecule visualization, and cryo-EM. The recent findings highlight the remarkable diversity of function among these structurally conserved proteins.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168814"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromatin Transcription Elongation - A Structural Perspective. 染色质转录延伸--结构视角。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-10-29 DOI: 10.1016/j.jmb.2024.168845

Lucas Farnung

{"title":"Chromatin Transcription Elongation - A Structural Perspective.","authors":"Lucas Farnung","doi":"10.1016/j.jmb.2024.168845","DOIUrl":"10.1016/j.jmb.2024.168845","url":null,"abstract":"In eukaryotic cells, transcription by RNA polymerase II occurs in the context of chromatin, requiring the transcription machinery to navigate through nucleosomes as it traverses gene bodies. Recent advances in structural biology have provided unprecedented insights into the mechanisms underlying transcription elongation. This review presents a structural perspective on transcription through chromatin, focusing on the latest findings from high-resolution structures of transcribing RNA polymerase II-nucleosome complexes. I discuss how RNA polymerase II, in concert with elongation factors such as SPT4/5, SPT6, ELOF1, and the PAF1 complex, engages with and transcribes through nucleosomes. The review examines the stepwise unwrapping of nucleosomal DNA as polymerase advances, the roles of elongation factors in facilitating this process, and the mechanisms of nucleosome retention and transfer during transcription. This structural perspective provides a foundation for understanding the intricate interplay between the transcription machinery and chromatin, offering insights into how cells balance the need for genetic accessibility with the maintenance of genome stability and epigenetic regulation.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168845"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fateful Decisions of Where to Cut the Line: Pathology Associated with Aberrant 3' End Processing and Transcription Termination. 决定在何处切断转录线的致命决定：与 3'末端异常处理和转录终止有关的病理学。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-09-24 DOI: 10.1016/j.jmb.2024.168802

Pawel Grzechnik, Hannah E Mischo

引用次数: 0

Mechanisms of RNA Polymerase II Termination at the 3'-End of Genes. RNA 聚合酶 II 在基因 3'- 端终止的机制。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-08-02 DOI: 10.1016/j.jmb.2024.168735

David Lopez Martinez, Jesper Q Svejstrup

{"title":"Mechanisms of RNA Polymerase II Termination at the 3'-End of Genes.","authors":"David Lopez Martinez, Jesper Q Svejstrup","doi":"10.1016/j.jmb.2024.168735","DOIUrl":"10.1016/j.jmb.2024.168735","url":null,"abstract":"RNA polymerase II (RNAPII) is responsible for the synthesis of a diverse set of RNA molecules, including protein-coding messenger RNAs (mRNAs) and many short non-coding RNAs (ncRNAs). For this purpose, RNAPII relies on a multitude of factors that regulate the transcription cycle, from initiation and promoter-proximal pausing, through elongation and finally termination. RNAPII transcription termination at the end of genes ensures the release of RNAPII from the DNA template and its efficient recycling for further rounds of transcription. Termination of RNAPII is tightly coupled to 3'-end mRNA processing, which constitutes an important trigger for the subsequent transcription termination event. In this review, we discuss the current understanding of RNAPII termination mechanisms, focusing on 'canonical' termination at the 3'-end of genes. We also integrate the allosteric and 'torpedo' models into a unified model of termination, and describe the different termination factors that have been identified to date, paying special attention to the human factors and their mechanism of action at the molecular level. Indeed, in recent years the development of novel approaches in structural biology, biochemistry and cell biology have together led to a more detailed comprehension of the different mechanisms of RNAPII termination, and a better understanding of their importance in regulating gene expression, especially under cellular stress and pathological situations.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168735"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple Forms and Functions of Premature Termination by RNA Polymerase II. RNA 聚合酶 II 提前终止的多种形式和功能。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-08-09 DOI: 10.1016/j.jmb.2024.168743

David L Bentley

{"title":"Multiple Forms and Functions of Premature Termination by RNA Polymerase II.","authors":"David L Bentley","doi":"10.1016/j.jmb.2024.168743","DOIUrl":"10.1016/j.jmb.2024.168743","url":null,"abstract":"Eukaryotic genomes are widely transcribed by RNA polymerase II (pol II) both within genes and in intergenic regions. POL II elongation complexes comprising the polymerase, the DNA template and nascent RNA transcript must be extremely processive in order to transcribe the longest genes which are over 1 megabase long and take many hours to traverse. Dedicated termination mechanisms are required to disrupt these highly stable complexes. Transcription termination occurs not only at the 3' ends of genes once a full length transcript has been made, but also within genes and in promiscuously transcribed intergenic regions. Termination at these latter positions is termed \"premature\" because it is not triggered in response to a specific signal that marks the 3' end of a gene, like a polyA site. One purpose of premature termination is to remove polymerases from intergenic regions where they are \"not wanted\" because they may interfere with transcription of overlapping genes or the progress of replication forks. Premature termination has recently been appreciated to occur at surprisingly high rates within genes where it is speculated to serve regulatory or quality control functions. In this review I summarize current understanding of the different mechanisms of premature termination and its potential functions.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168743"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The HIV-1 Transcriptional Program: From Initiation to Elongation Control. HIV-1 转录程序：从启动到延伸控制

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-06-25 DOI: 10.1016/j.jmb.2024.168690

Iván D'Orso

{"title":"The HIV-1 Transcriptional Program: From Initiation to Elongation Control.","authors":"Iván D'Orso","doi":"10.1016/j.jmb.2024.168690","DOIUrl":"10.1016/j.jmb.2024.168690","url":null,"abstract":"A large body of work in the last four decades has revealed the key pillars of HIV-1 transcription control at the initiation and elongation steps. Here, I provide a recount of this collective knowledge starting with the genomic elements (DNA and nascent TAR RNA stem-loop) and transcription factors (cellular and the viral transactivator Tat), and later transitioning to the assembly and regulation of transcription initiation and elongation complexes, and the role of chromatin structure. Compelling evidence support a core HIV-1 transcriptional program regulated by the sequential and concerted action of cellular transcription factors and Tat to promote initiation and sustain elongation, highlighting the efficiency of a small virus to take over its host to produce the high levels of transcription required for viral replication. I summarize new advances including the use of CRISPR-Cas9, genetic tools for acute factor depletion, and imaging to study transcriptional dynamics, bursting and the progression through the multiple phases of the transcriptional cycle. Finally, I describe current challenges to future major advances and discuss areas that deserve more attention to both bolster our basic knowledge of the core HIV-1 transcriptional program and open up new therapeutic opportunities.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"168690"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Controlling Transcription Elongation and Termination: More Than a Means to An End.

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-11-26 DOI: 10.1016/j.jmb.2024.168886

Stephen Buratowski, Karen M Arndt

引用次数: 0

Pause Patrol: Negative Elongation Factor's Role in Promoter-Proximal Pausing and Beyond. 暂停巡逻队：负延伸因子在启动子-近端暂停及其他过程中的作用

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-01-01 Epub Date: 2024-09-04 DOI: 10.1016/j.jmb.2024.168779

Annette J Diao, Bonnie G Su, Seychelle M Vos

引用次数: 0