Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"Crosstalk between circular RNAs and the STAT3 signaling pathway in human cancer","authors":"Mansour Almouh ,&nbsp;Chadi Soukkarieh ,&nbsp;Morshed Kassouha ,&nbsp;Samer Ibrahim","doi":"10.1016/j.bbagrm.2024.195051","DOIUrl":"10.1016/j.bbagrm.2024.195051","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are endogenous covalently closed single-stranded RNAs produced by reverse splicing of pre-mRNA. Emerging evidence suggests that circRNAs contribute to cancer progression by modulating the oncogenic STAT3 signaling pathway, which plays key roles in human malignancies. STAT3 signaling-related circRNAs expression appears to be extensively dysregulated in diverse cancer types, where they function either as tumor suppressors or oncogenes. However, the biological effects of STAT3 signaling-related circRNAs and their associations with cancer have not been systematically studied before. Given this, shedding light on the interaction between circRNAs and STAT3 signaling pathway in human malignancies may provide several novel insights into cancer therapy. In this review, we provide a comprehensive introduction to the molecular mechanisms by which circRNAs regulate STAT3 signaling in cancer progression, and the crosstalk between STAT3 signaling-related circRNAs and other signaling pathways. We also further discuss the role of the circRNA/STAT3 axis in cancer chemotherapy sensitivity.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 4","pages":"Article 195051"},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human ARMC6 binds in vitro to both cancer genes and telomeric RNA, favoring G-quadruplex structure recognition","authors":"Matej Adámik ,&nbsp;Zuzana Soldánová ,&nbsp;Magdaléna Drotárová ,&nbsp;Katarína Brečková ,&nbsp;Marek Petr ,&nbsp;Robert Helma ,&nbsp;Leon P. Jenner ,&nbsp;Michaela Vorlíčková ,&nbsp;Eva Sýkorová ,&nbsp;Marie Brázdová","doi":"10.1016/j.bbagrm.2024.195050","DOIUrl":"10.1016/j.bbagrm.2024.195050","url":null,"abstract":"<div><p>Armadillo repeat-containing proteins (ARMCs) are a large family found throughout eukaryotes, which play prominent roles in cell adhesion, signaling and cytoskeletal regulation. The ARMC6 protein is highly conserved in primates, including humans, but to date does not have a clear function beyond initial hints of a link to cancer and telomerase activity. We report here in vitro experiments showing ARMC6 binding to DNA promoter sequences from several cancer-related genes (e.g., <em>EGFR</em>, <em>VEGF</em> and c-<em>MYC)</em>, and also to the telomeric RNA repeat (TERRA). ARMC6 binding activity appears to recognize G-quadruplex motifs, which are being increasingly implicated as structure-based protein binding sites in chromosome maintenance and repair. In vivo investigation of ARMC6 function revealed that when this protein is overexpressed in human cell lines, there is different expression of genes connected with oncogenic pathways and those implicated in downstream non-canonical telomerase pathways (e.g., <em>VEGF</em>, <em>hTERT,</em> c-<em>MYC</em>, <em>ESM1</em>, <em>MMP3</em>). ARMC6 is already known to interact with human shelterin protein TRF2 and telomerase. The protein binds G-quadruplex structures and does so preferentially to RNA over DNA. As such, this protein may be an example of how a non-canonical nucleic acid structural motif allows mediation between gene regulation and telomeric chromatin rearrangement pathways.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195050"},"PeriodicalIF":2.6,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cut from the same cloth: RNAs transcribed from regulatory elements","authors":"E.M. Stasevich ,&nbsp;A.V. Simonova ,&nbsp;E.A. Bogomolova ,&nbsp;M.M. Murashko ,&nbsp;A.N. Uvarova ,&nbsp;E.A. Zheremyan ,&nbsp;K.V. Korneev ,&nbsp;A.M. Schwartz ,&nbsp;D.V. Kuprash ,&nbsp;D.E. Demin","doi":"10.1016/j.bbagrm.2024.195049","DOIUrl":"10.1016/j.bbagrm.2024.195049","url":null,"abstract":"<div><p>A certain degree of chromatin openness is necessary for the activity of transcription-regulating regions within the genome, facilitating accessibility to RNA polymerases and subsequent synthesis of regulatory element RNAs (regRNAs) from these regions. The rapidly increasing number of studies underscores the significance of regRNAs across diverse cellular processes and diseases, challenging the paradigm that these transcripts are non-functional transcriptional noise. This review explores the multifaceted roles of regRNAs in human cells, encompassing rather well-studied entities such as promoter RNAs and enhancer RNAs (eRNAs), while also providing insights into overshadowed silencer RNAs and insulator RNAs. Furthermore, we assess notable examples of shorter regRNAs, like miRNAs, snRNAs, and snoRNAs, playing important roles. Expanding our discourse, we deliberate on the potential usage of regRNAs as biomarkers and novel targets for cancer and other human diseases.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195049"},"PeriodicalIF":2.6,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3K56 acetylation affects Candida albicans morphology and secreted soluble factors interacting with the host","authors":"Marisa Conte ,&nbsp;Daniela Eletto ,&nbsp;Martina Pannetta ,&nbsp;Roberta Esposito ,&nbsp;Maria Chiara Monti ,&nbsp;Elva Morretta ,&nbsp;Peter Tessarz ,&nbsp;Silvana Morello ,&nbsp;Alessandra Tosco ,&nbsp;Amalia Porta","doi":"10.1016/j.bbagrm.2024.195048","DOIUrl":"10.1016/j.bbagrm.2024.195048","url":null,"abstract":"<div><p>In recent years, epigenetics has been revealed as a mechanism able to modulate the expression of virulence traits in diverse pathogens, including <em>Candida albicans</em>. Indeed, epigenetic regulation can sense environmental changes, leading to the rapid and reversible modulation of gene expression with consequent adaptation to novel environments. How epigenetic changes can impact expression and signalling output, including events associated with mechanisms of morphological transition and virulence, is still poorly studied. Here, using nicotinamide as a sirtuin inhibitor, we explored how the accumulation of the H3K56 acetylation, the most prominent histone acetylation in <em>C. albicans</em>, might affect its interaction with the host. Our experiments demonstrate that H3K56 acetylation profoundly affects the production and/or secretion of soluble factors compromising actin remodelling and cytokine production. ChIP- and RNA-seq analyses highlighted a direct impact of H3K56 acetylation on genes related to phenotypic switching, biofilm formation and cell aggregation. Direct and indirect regulation also involves genes related to cell wall protein biosynthesis, β-glucan and mannan exposure, and hydrolytic secreted enzymes, supporting the hypothesis that the fluctuations of H3K56 acetylation in <em>C. albicans</em> might impair the macrophage response to the yeast and thus promote the host-immune escaping.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195048"},"PeriodicalIF":2.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1874939924000440/pdfft?md5=8b63a578c5baa7bc3e34cab1b99bd9b7&pid=1-s2.0-S1874939924000440-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incautious design of shRNAs for stable overexpression of miRNAs could result in generation of undesired isomiRs","authors":"Diana Maltseva ,&nbsp;Ivan Kirillov ,&nbsp;Anton Zhiyanov ,&nbsp;Daria Averinskaya ,&nbsp;Roman Suvorov ,&nbsp;Daria Gubani ,&nbsp;Anna Kudriaeva ,&nbsp;Alexey Belogurov Jr ,&nbsp;Alexander Tonevitsky","doi":"10.1016/j.bbagrm.2024.195046","DOIUrl":"10.1016/j.bbagrm.2024.195046","url":null,"abstract":"<div><p>shRNA-mediated strategy of miRNA overexpression based on RNA Polymerase III (Pol III) expression cassettes is widely used for miRNA functional studies. For some miRNAs, e.g., encoded in the genome as a part of a polycistronic miRNA cluster, it is most likely the only way for their individual stable overexpression. Here we have revealed that expression of miRNAs longer than 19 nt (e.g. 23 nt in length hsa-miR-93-5p) using such approach could be accompanied by undesired predominant generation of 5′ end miRNA isoforms (5′-isomiRs). Extra U residues (up to five) added by Pol III at the 3′ end of the transcribed shRNA during transcription termination could cause a shift in the Dicer cleavage position of the shRNA. This results in the formation of 5′-isomiRs, which have a significantly altered seed region compared to the initially encoded canonical hsa-miR-93-5p. We demonstrated that the commonly used qPCR method is insensitive to the formation of 5′-isomiRs and cannot be used to confirm miRNA overexpression. However, the predominant expression of 5′-isomiRs without three or four first nucleotides instead of the canonical isoform could be disclosed based on miRNA-Seq analysis. Moreover, mRNA sequencing data showed that the 5′-isomiRs of hsa-miR-93-5p presumably regulate their own mRNA targets. Thus, omitting miRNA-Seq analysis may lead to erroneous conclusions regarding revealed mRNA targets and possible molecular mechanisms in which studied miRNA is involved. Overall, the presented results show that structures of shRNAs for stable overexpression of miRNAs requires careful design to avoid generation of undesired 5′-isomiRs.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195046"},"PeriodicalIF":4.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HBO1, a MYSTerious KAT and its links to cancer","authors":"Akihiko Yokoyama ,&nbsp;Hiroyuki Niida ,&nbsp;Tatiana G. Kutateladze ,&nbsp;Jacques Côté","doi":"10.1016/j.bbagrm.2024.195045","DOIUrl":"10.1016/j.bbagrm.2024.195045","url":null,"abstract":"<div><p>The histone acetyltransferase HBO1, also known as KAT7, is a major chromatin modifying enzyme responsible for H3 and H4 acetylation. It is found within two distinct tetrameric complexes, the JADE subunit-containing complex and BRPF subunit-containing complex. The HBO1-JADE complex acetylates lysine 5, 8 and 12 of histone H4, and the HBO1-BRPF complex acetylates lysine 14 of histone H3. HBO1 regulates gene transcription, DNA replication, DNA damage repair, and centromere function. It is involved in diverse signaling pathways and plays crucial roles in development and stem cell biology. Recent work has established a strong relationship of HBO1 with the histone methyltransferase MLL/KMT2A in acute myeloid leukemia. Here, we discuss functional and pathological links of HBO1 to cancer, highlighting the underlying mechanisms that may pave the way to the development of novel anti-cancer therapies.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195045"},"PeriodicalIF":4.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone ubiquitination: Role in genome integrity and chromatin organization","authors":"Nikhil Baban Ghate ,&nbsp;Kaustubh Sanjay Nadkarni ,&nbsp;Ganesh Kumar Barik ,&nbsp;Sharad Shriram Tat ,&nbsp;Osheen Sahay ,&nbsp;Manas Kumar Santra","doi":"10.1016/j.bbagrm.2024.195044","DOIUrl":"10.1016/j.bbagrm.2024.195044","url":null,"abstract":"<div><p>Maintenance of genome integrity is a precise but tedious and complex job for the cell. Several post-translational modifications (PTMs) play vital roles in maintaining the genome integrity. Although ubiquitination is one of the most crucial PTMs, which regulates the localization and stability of the nonhistone proteins in various cellular and developmental processes, ubiquitination of the histones is a pivotal epigenetic event critically regulating chromatin architecture. In addition to genome integrity, importance of ubiquitination of core histones (H2A, H2A, H3, and H4) and linker histone (H1) have been reported in several cellular processes. However, the complex interplay of histone ubiquitination and other PTMs, as well as the intricate chromatin architecture and dynamics, pose a significant challenge to unravel how histone ubiquitination safeguards genome stability. Therefore, further studies are needed to elucidate the interactions between histone ubiquitination and other PTMs, and their role in preserving genome integrity. Here, we review all types of histone ubiquitinations known till date in maintaining genomic integrity during transcription, replication, cell cycle, and DNA damage response processes. In addition, we have also discussed the role of histone ubiquitination in regulating other histone PTMs emphasizing methylation and acetylation as well as their potential implications in chromatin architecture. Further, we have also discussed the involvement of deubiquitination enzymes (DUBs) in controlling histone ubiquitination in modulating cellular processes.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195044"},"PeriodicalIF":4.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"To Ub or not to Ub: The epic dilemma of histones that regulate gene expression and epigenetic cross-talk","authors":"Anirban Dasgupta ,&nbsp;Sandhik Nandi ,&nbsp;Sayan Gupta ,&nbsp;Siddhartha Roy ,&nbsp;Chandrima Das","doi":"10.1016/j.bbagrm.2024.195033","DOIUrl":"10.1016/j.bbagrm.2024.195033","url":null,"abstract":"<div><p>A dynamic array of histone post-translational modifications (PTMs) regulate diverse cellular processes in the eukaryotic chromatin. Among them, histone ubiquitination is particularly complex as it alters nucleosome surface area fostering intricate cross-talk with other chromatin modifications. Ubiquitin signaling profoundly impacts DNA replication, repair, and transcription. Histones can undergo varied extent of ubiquitination such as mono, multi-mono, and polyubiquitination, which brings about distinct cellular fates. Mechanistic studies of the ubiquitin landscape in chromatin have unveiled a fascinating tapestry of events that orchestrate gene regulation. In this review, we summarize the key contributors involved in mediating different histone ubiquitination and deubiquitination events, and discuss their mechanism which impacts cell transcriptional identity and DNA damage response. We also focus on the proteins bearing epigenetic reader modules critical in discerning site-specific histone ubiquitination, pivotal for establishing complex epigenetic crosstalk. Moreover, we highlight the role of histone ubiquitination in different human diseases including neurodevelopmental disorders and cancer. Overall the review elucidates the intricate orchestration of histone ubiquitination impacting diverse cellular functions and disease pathogenesis, and provides insights into the current challenges of targeting them for therapeutic interventions.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195033"},"PeriodicalIF":4.7,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulation of Znt family members znt4, znt5 and znt10 and their function in zinc transport in yellow catfish (Pelteobagrus fulvidraco)","authors":"Lu-Lu Liu ,&nbsp;Chang-Chun Song ,&nbsp;Nermeen Abu-Elala ,&nbsp;Xiao-Ying Tan ,&nbsp;Tao Zhao ,&nbsp;Hua Zheng ,&nbsp;Hong Yang ,&nbsp;Zhi Luo","doi":"10.1016/j.bbagrm.2024.195041","DOIUrl":"10.1016/j.bbagrm.2024.195041","url":null,"abstract":"<div><p>The study characterized the transcriptionally regulatory mechanism and functions of three zinc (Zn) transporters (<em>znt4</em>, <em>znt5</em> and <em>znt10</em>) in Zn²⁺ metabolism in yellow catfish (<em>Pelteobagrus fulvidraco</em>), commonly freshwater fish in China and other countries. We cloned the sequences of <em>znt4</em> promoter, spanning from −1217 bp to +80 bp relative to TSS (1297 bp); <em>znt5</em>, spanning from −1783 bp to +49 bp relative to TSS (1832 bp) and <em>znt10</em>, spanning from −1923 bp to +190 bp relative to TSS (2113 bp). In addition, after conducting the experiments of sequential deletion of promoter region and mutation of potential binding site, we found that the Nrf2 binding site (−607/−621 bp) and Klf4 binding site (−5/−14 bp) were required on <em>znt4</em> promoter, the Mtf-1 binding site (−1674/−1687 bp) and Atf4 binding site (−444/−456 bp) were required on <em>znt5</em> promoter and the Atf4 binding site (−905/−918 bp) was required on <em>znt10</em> promoter. Then, according to EMSA and ChIP, we found that Zn²⁺ incubation increased DNA affinity of Atf4 to <em>znt5</em> or <em>znt10</em> promoter, but decreased DNA affinity of Nrf2 to <em>znt4</em> promoter, Klf4 to <em>znt4</em> promoter and Mtf-1 to <em>znt5</em> promoter. Using fluorescent microscopy, it was revealed that Znt4 and Znt10 were located in the lysosome and Golgi, and Znt5 was located in the Golgi. Finally, we found that <em>znt4</em> knockdown reduced the zinc content of lysosome and Golgi in the control and zinc-treated group; <em>znt5</em> knockdown reduced the zinc content of Golgi in the control and zinc-treated group and <em>znt10</em> knockdown reduced the zinc content of Golgi in the zinc-treated group. High dietary zinc supplement up-regulated Znt4 and Znt5 protein expression. Above all, for the first time, we revealed that Klf4 and Nrf2 transcriptionally regulated the activities of <em>znt4</em> promoter; Mtf-1 and Atf4 transcriptionally regulated the activities of <em>znt5</em> promoter and Atf4 transcriptionally regulated the activities of <em>znt10</em> promoter, which provided innovative regulatory mechanism of zinc transporting in yellow catfish. Our study also elucidated their subcellular location, and regulatory role of zinc homeostasis in yellow catfish.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 3","pages":"Article 195041"},"PeriodicalIF":4.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key interactions of RNA polymerase with 6S RNA and secondary channel factors during pRNA synthesis","authors":"Ivan Petushkov ,&nbsp;Daria Elkina ,&nbsp;Olga Burenina ,&nbsp;Elena Kubareva ,&nbsp;Andrey Kulbachinskiy","doi":"10.1016/j.bbagrm.2024.195032","DOIUrl":"https://doi.org/10.1016/j.bbagrm.2024.195032","url":null,"abstract":"<div><p>Small non-coding 6S RNA mimics DNA promoters and binds to the σ⁷⁰ holoenzyme of bacterial RNA polymerase (RNAP) to suppress transcription of various genes mainly during the stationary phase of cell growth or starvation. This inhibition can be relieved upon synthesis of short product RNA (pRNA) performed by RNAP from the 6S RNA template. Here, we have shown that pRNA synthesis depends on specific contacts of 6S RNA with RNAP and interactions of the σ finger with the RNA template in the active site of RNAP, and is also modulated by the secondary channel factors. We have adapted a molecular beacon assay with fluorescently labeled σ⁷⁰ to analyze 6S RNA release during pRNA synthesis. We found the kinetics of 6S RNA release to be oppositely affected by mutations in the σ finger and in the CRE pocket of core RNAP, similarly to the reported role of these regions in promoter-dependent transcription. Secondary channel factors, DksA and GreB, inhibit pRNA synthesis and 6S RNA release from RNAP, suggesting that they may contribute to the 6S RNA-mediated switch in transcription during stringent response. Our results demonstrate that pRNA synthesis depends on a similar set of contacts between RNAP and 6S RNA as in the case of promoter-dependent transcription initiation and reveal that both processes can be regulated by universal transcription factors acting on RNAP.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195032"},"PeriodicalIF":4.7,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}