Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"LncRNA-mediated orchestrations of alternative splicing in the landscape of breast cancer","authors":"Samarth Kansara ,&nbsp;Prajwali Sawant ,&nbsp;Taranjeet Kaur ,&nbsp;Manoj Garg ,&nbsp;Amit Kumar Pandey","doi":"10.1016/j.bbagrm.2024.195017","DOIUrl":"10.1016/j.bbagrm.2024.195017","url":null,"abstract":"<div><p>Alternative splicing (AS) is a fundamental post-transcriptional process in eukaryotes, enabling a single gene to generate diverse mRNA transcripts, thereby enhancing protein variability. This process involves the excision of introns and the joining of exons in pre-mRNA(s) to form mature mRNA. The resulting mature mRNAs exhibit various combinations of exons, contributing to functional diversity. Dysregulation of AS can substantially modulate protein functions, impacting the onset and progression of numerous diseases, including cancer. Non-coding RNAs (ncRNAs) are distinct from protein-coding RNAs and consist of short and long types. Long non-coding RNAs (lncRNAs) play an important role in regulating several cellular processes, particularly alternative splicing, according to new research. This review provides insight into the latest discoveries concerning how lncRNAs influence alternative splicing within the realm of breast cancer. Additionally, it explores potential therapeutic strategies focused on targeting lncRNAs.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195017"},"PeriodicalIF":4.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716589","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":"An epitope-tagged Swd2 reveals the different requirements of Swd2 concentration in H3K4 methylation and viability","authors":"Junsoo Oh ,&nbsp;Seho Kim ,&nbsp;SangMyung Kim ,&nbsp;Jueun Kim ,&nbsp;Soojin Yeom ,&nbsp;Jung-Shin Lee","doi":"10.1016/j.bbagrm.2024.195009","DOIUrl":"10.1016/j.bbagrm.2024.195009","url":null,"abstract":"<div><p>Swd2/Cps35 is a common component of the COMPASS H3K4 methyltransferase and CPF transcription termination complex in <em>Saccharomyces cerevisiae</em>. The deletion of <em>SWD2</em> is lethal, which results from transcription termination defects in snoRNA genes. This study isolated a yeast strain that showed significantly reduced protein level of Swd2 following epitope tagging at its N-terminus (<em>9MYC-SWD2</em>). The reduced level of Swd2 in the <em>9MYC-SWD2</em> strain was insufficient for the stability of the Set1 H3K4 methyltransferase, H3K4me3 and snoRNA termination, but the level was enough for viability and growth similar to the wildtype strain. In addition, we presented the genes differentially regulated by the essential protein Swd2 under optimal culture conditions for the first time. The expression of genes known to be decreased in the absence of Set1 and H3K4me3, including NAD biosynthetic process genes and histone genes, was decreased in the <em>9MYC-SWD2</em> strain, as expected. However, the effects of Swd2 on the ribosome biogenesis (RiBi) genes were opposite to those of Set1, suggesting that the expression of RiBi genes is regulated by more complex relationship between COMPASS and other Swd2-containing complexes. These data suggest that different concentrations of Swd2 are required for its roles in H3K4me3 and viability and that it may be either contributory or contrary to the transcriptional regulation of Set1/H3K4me3, depending on the gene group.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195009"},"PeriodicalIF":4.7,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708562","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 H2B ubiquitylation: Connections to transcription and effects on chromatin structure","authors":"Tasniem Fetian,&nbsp;Aakash Grover,&nbsp;Karen M. Arndt","doi":"10.1016/j.bbagrm.2024.195018","DOIUrl":"10.1016/j.bbagrm.2024.195018","url":null,"abstract":"<div><p>Nucleosomes are major determinants of eukaryotic genome organization and regulation. Many studies, incorporating a diversity of experimental approaches, have been focused on identifying and discerning the contributions of histone post-translational modifications to DNA-centered processes. Among these, monoubiquitylation of H2B (H2Bub) on K120 in humans or K123 in budding yeast is a critical histone modification that has been implicated in a wide array of DNA transactions. H2B is co-transcriptionally ubiquitylated and deubiquitylated via the concerted action of an extensive network of proteins. In addition to altering the chemical and physical properties of the nucleosome, H2Bub is important for the proper control of gene expression and for the deposition of other histone modifications. In this review, we discuss the molecular mechanisms underlying the ubiquitylation cycle of H2B and how it connects to the regulation of transcription and chromatin structure.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 2","pages":"Article 195018"},"PeriodicalIF":4.7,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708563","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":"Influence of cell volume on the gene transcription rate","authors":"José E. Pérez-Ortín ,&nbsp;María J. García-Marcelo ,&nbsp;Irene Delgado-Román ,&nbsp;María C. Muñoz-Centeno ,&nbsp;Sebastián Chávez","doi":"10.1016/j.bbagrm.2024.195008","DOIUrl":"10.1016/j.bbagrm.2024.195008","url":null,"abstract":"<div><p><span>Cells vary in volume throughout their life cycle and in many other circumstances, while their genome remains identical. Hence, the RNA production factory must adapt to changing needs, while maintaining the same production lines. This paradox is resolved by different mechanisms in distinct cells and circumstances. RNA polymerases have evolved to cope with the particular circumstances of each case and the different characteristics of the several RNA molecule types, especially their stabilities. Here we review current knowledge on these issues. We focus on the yeast </span><span><em>Saccharomyces cerevisiae</em></span>, where many of the studies have been performed, although we compare and discuss the results obtained in other eukaryotes and propose several ideas and questions to be tested and solved in the future.</p></div><div><h3>Take away</h3><p></p><ul><li><span>−</span><span><p>The mRNA synthesis rate can be influenced by cell volume, and vice versa</p></span></li><li><span>−</span><span><p>Transcription and degradation rates must compensate reciprocally to maintain RNA homeostasis</p></span></li><li><span>−</span><span><p>Different cells and RNAs with diverse stabilities use distinct regulatory mechanisms</p></span></li><li><span>−</span><span><p>Asymmetrical division requires alternative transcription rate regulation with volume</p></span></li></ul></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195008"},"PeriodicalIF":4.7,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514307","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":"Post-translational regulation of the mTORC1 pathway: A switch that regulates metabolism-related gene expression","authors":"Yitao Wang ,&nbsp;Tobias Engel ,&nbsp;Xinchen Teng","doi":"10.1016/j.bbagrm.2024.195005","DOIUrl":"10.1016/j.bbagrm.2024.195005","url":null,"abstract":"<div><p><span><span><span><span>The mechanistic target of rapamycin complex 1 (mTORC1) is a kinase complex that plays a crucial role in coordinating cell growth in response to various signals, including </span>amino acids, growth factors, oxygen, and ATP. Activation of mTORC1 promotes cell growth and </span>anabolism, while its suppression leads to catabolism and inhibition of cell growth, enabling cells to withstand nutrient scarcity and stress. Dysregulation of mTORC1 activity is associated with numerous diseases, such as cancer, </span>metabolic disorders<span>, and neurodegenerative conditions. This review focuses on how post-translational modifications, particularly phosphorylation and ubiquitination, modulate mTORC1 </span></span>signaling pathway and their consequential implications for pathogenesis. Understanding the impact of phosphorylation and ubiquitination on the mTORC1 signaling pathway provides valuable insights into the regulation of cellular growth and potential therapeutic targets for related diseases.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195005"},"PeriodicalIF":4.7,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500071","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":"Targeting ‘histone mark’: Advanced approaches in epigenetic regulation of telomere dynamics in cancer","authors":"Ankita Das ,&nbsp;Ashok K. Giri ,&nbsp;Pritha Bhattacharjee","doi":"10.1016/j.bbagrm.2024.195007","DOIUrl":"10.1016/j.bbagrm.2024.195007","url":null,"abstract":"<div><p><span><span>Telomere integrity is required for the maintenance of </span>genome stability<span> and prevention of oncogenic transformation of cells. Recent evidence suggests the presence of epigenetic modifications<span> as an important regulator of mammalian telomeres. Telomeric and subtelomeric regions are rich in epigenetic marks that regulate </span></span></span>telomere length<span><span> majorly through DNA methylation and post-translational histone modifications. Specific </span>histone modifying enzymes<span><span> play an integral role in establishing telomeric histone codes<span> necessary for the maintenance of structural integrity. Alterations of crucial histone moieties and histone modifiers cause deregulations in the telomeric chromatin leading to carcinogenic manifestations. This review delves into the significance of histone modifications and their influence on telomere dynamics concerning cancer. Additionally, it highlights the existing research gaps that hold the potential to drive the development of therapeutic interventions targeting the telomere </span></span>epigenome.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195007"},"PeriodicalIF":4.7,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492283","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":"Prospects and challenges of noncoding-RNA-mediated inhibition of heat shock protein 90 for cancer therapy","authors":"Shria Mattoo ,&nbsp;Abha Gupta ,&nbsp;Manvee Chauhan ,&nbsp;Akshi Agrawal ,&nbsp;Subrata Kumar Pore","doi":"10.1016/j.bbagrm.2024.195006","DOIUrl":"10.1016/j.bbagrm.2024.195006","url":null,"abstract":"<div><p><span><span>Heat Shock Protein 90 (HSP90) is a potential drug target for cancer therapy as it is often dysregulated in several cancers, including lung, breast, pancreatic, and prostate cancers. In cancer, HSP90 fails to maintain the structural and functional integrity of its several client proteins which are involved in the hallmarks of cancer such as </span>cell proliferation<span><span>, invasion, migration, angiogenesis, and apoptosis. Several </span>small molecule<span><span> inhibitors of HSP90 have been shown to exhibit anticancer effects in vitro and in vivo </span>animal models. However, a few of them are currently under clinical studies. The status and potential limitations of these inhibitors are discussed here. Studies demonstrate that several noncoding </span></span></span>RNAs<span> (ncRNAs) such as microRNAs<span> (miRNAs) and long noncoding RNAs<span> (lncRNAs) regulate HSP90 and its client proteins to modulate cellular processes to exhibit oncogenic or tumor suppressing properties. Over the last decade, miRNAs and lncRNAs have drawn significant interest from the scientific community as therapeutic agents or targets for clinical applications. Here, we discuss the detailed mechanistic regulation of HSP90 and its client proteins by ncRNAs. Moreover, we highlight the significance of these ncRNAs as potential therapeutic agents/targets, and the challenges associated with ncRNA-based therapies. This article aims to provide a holistic view on HSP90-regulating ncRNAs for the development of novel therapeutic strategies to combat cancer.</span></span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195006"},"PeriodicalIF":4.7,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139465448","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":"Insight into the mechanism of AML del(9q) progression: hnRNP K targets the myeloid master regulators CEBPA (C/EBPα) and SPI1 (PU.1)","authors":"Kerstin Rahn ,&nbsp;Ali T. Abdallah ,&nbsp;Lin Gan ,&nbsp;Shelley Herbrich ,&nbsp;Roland Sonntag ,&nbsp;Oscar Benitez ,&nbsp;Prerna Malaney ,&nbsp;Xiaorui Zhang ,&nbsp;Ashely G. Rodriguez ,&nbsp;Jared Brottem ,&nbsp;Gernot Marx ,&nbsp;Tim H. Brümmendorf ,&nbsp;Dirk H. Ostareck ,&nbsp;Antje Ostareck-Lederer ,&nbsp;Martina Crysandt ,&nbsp;Sean M. Post ,&nbsp;Isabel S. Naarmann-de Vries","doi":"10.1016/j.bbagrm.2023.195004","DOIUrl":"10.1016/j.bbagrm.2023.195004","url":null,"abstract":"<div><p><span>Deletions on the long arm of chromosome 9 (del(9q)) are recurrent abnormalities in about 2 % of acute myeloid leukemia cases, which usually involve </span><em>HNRNPK</em> and are frequently associated with other known aberrations. Based on an <em>Hnrnpk</em> haploinsufficient mouse model, a recent study demonstrated a function of hnRNP K in pathogenesis of myeloid malignancies <em>via</em><span><span> the regulation of cellular proliferation<span> and myeloid differentiation programs. Here, we provide evidence that reduced hnRNP K expression results in the dysregulated expression of C/EBPα and additional transcription factors. CyTOF analysis revealed monocytic skewing with increased levels of mature myeloid cells. To explore the role of hnRNP K during normal and pathological myeloid differentiation in humans, we characterized hnRNP K-interacting </span></span>RNAs<span> in human AML cell lines. Notably, RNA-sequencing revealed several mRNAs encoding key transcription factors involved in the regulation of myeloid differentiation as targets of hnRNP K. We showed that specific sequence motifs confer the interaction of </span></span><span><em>SPI1</em></span> and <span><em>CEBPA</em></span><span> 5′ and 3′UTRs with hnRNP K. The siRNA mediated reduction of hnRNP K in human AML cells resulted in an increase of PU.1 and C/EBPα that is most pronounced for the p30 isoform. The combinatorial treatment with the inducer of myeloid differentiation valproic acid resulted in increased C/EBPα expression and myeloid differentiation. Together, our results indicate that hnRNP K post-transcriptionally regulates the expression of myeloid master transcription factors. These novel findings can inaugurate novel options for targeted treatment of AML del(9q) by modulation of hnRNP K function.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195004"},"PeriodicalIF":4.7,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441701","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":"Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation","authors":"Kanupriya Jha ,&nbsp;Amit Kumar ,&nbsp;Kartik Bhatnagar ,&nbsp;Anupam Patra ,&nbsp;Neel Sarovar Bhavesh ,&nbsp;Bipin Singh ,&nbsp;Sarika Chaudhary","doi":"10.1016/j.bbagrm.2023.195003","DOIUrl":"10.1016/j.bbagrm.2023.195003","url":null,"abstract":"<div><p><span>Post-translational modifications (PTMs) of transcription factors regulate transcriptional activity and play a key role in essentially all biological processes<span><span> and generate indispensable insight towards biological function including activity state, subcellular localization, protein solubility, protein folding, substrate trafficking, and protein-protein interactions. </span>Amino acids modified chemically via PTMs, function as molecular switches and affect the protein function and characterization and increase the </span></span>proteome<span><span> complexity. Krüppel-like transcription factors (KLFs) control essential cellular processes including proliferation, differentiation, migration, programmed cell death and various cancer-relevant processes. We investigated the interactions of KLF group-2 members with their binding partners to assess the role of acetylation and phosphorylation in KLFs on their </span>binding affinity. It was observed that acetylation and phosphorylation at different positions in KLFs have a variable effect on binding with specific partners. KLF2-EP300, KLF4-SP1, KLF6-ATF3, KLF6-JUN, and KLF7-JUN show stabilization upon acetylation or phosphorylation at variable positions. On the other hand, KLF4-CBP, KLF4-EP300, KLF5-CBP, KLF5-WWP1, KLF6-SP1, and KLF7-ATF3 show stabilization or destabilization due to acetylation or phosphorylation at variable positions in KLFs. This provides a molecular explanation of the experimentally observed dual role of KLF group-2 members as a suppressor or activator of cancers in a PTM-dependent manner.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195003"},"PeriodicalIF":4.7,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296626","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":"The association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae","authors":"Abel Cuevas-Bermúdez ,&nbsp;Verónica Martínez-Fernández ,&nbsp;Ana I. Garrido-Godino ,&nbsp;Antonio Jordán-Pla ,&nbsp;Xenia Peñate ,&nbsp;Manuel Martín-Expósito ,&nbsp;Gabriel Gutiérrez ,&nbsp;Chhabi K. Govind ,&nbsp;Sebastián Chávez ,&nbsp;Vicent Pelechano ,&nbsp;Francisco Navarro","doi":"10.1016/j.bbagrm.2023.194995","DOIUrl":"10.1016/j.bbagrm.2023.194995","url":null,"abstract":"<div><p><span>The tripartite interaction between the chromatin remodeler complex RSC, RNA<span><span> polymerase subunit Rpb5 and prefoldin-like Bud27 is necessary for proper RNA pol II elongation. Indeed lack of Bud27 alters this association and affects transcription elongation. This work investigates the consequences of lack of Bud27 on the chromatin association of RSC and RNA pol II, and on </span>nucleosome positioning. Our results demonstrate that RSC binds chromatin in gene bodies and lack of Bud27 alters this association, mainly around polyA sites. This alteration impacts chromatin organization and leads to the accumulation of RNA pol II molecules around polyA sites, likely due to pausing or arrest. Our data suggest that RSC is necessary to maintain chromatin organization around those sites, and any alteration of this organization results in the widespread use of alternative polyA sites. Finally, we also find a similar molecular phenotype that occurs upon TOR inhibition with rapamycin, which suggests that alternative </span></span>polyadenylation observed upon TOR inhibition is likely Bud27-dependent.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 194995"},"PeriodicalIF":4.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650487","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}