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

IF 2.6 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-13 DOI:10.1016/j.bbagrm.2023.194995
Abel Cuevas-Bermúdez , Verónica Martínez-Fernández , Ana I. Garrido-Godino , Antonio Jordán-Pla , Xenia Peñate , Manuel Martín-Expósito , Gabriel Gutiérrez , Chhabi K. Govind , Sebastián Chávez , Vicent Pelechano , Francisco Navarro
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Abstract

The tripartite interaction between the chromatin remodeler complex RSC, RNA 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 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 polyadenylation observed upon TOR inhibition is likely Bud27-dependent.

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RSC重塑复合体与染色质的关联受前折叠蛋白样Bud27的影响,并决定了酿酒酵母中核小体的定位和聚腺苷化位点的使用。
染色质重塑复合体RSC、RNA聚合酶亚基Rpb5和前折叠蛋白样Bud27之间的三重相互作用是RNA pol II适当延伸所必需的。事实上,Bud27的缺失改变了这种关联并影响了转录伸长。这项工作研究了缺乏Bud27对RSC和RNA pol II的染色质关联以及核小体定位的影响。我们的研究结果表明,RSC与基因体中的染色质结合,缺乏Bud27会改变这种结合,主要是在polyA位点附近。这种改变影响染色质组织,并导致RNA pol II分子在polyA位点周围积聚,可能是由于暂停或阻滞。我们的数据表明RSC对于维持这些位点周围的染色质组织是必要的,并且这种组织的任何改变都会导致替代聚a位点的广泛使用。最后,我们还发现类似的分子表型发生在雷帕霉素抑制TOR时,这表明在TOR抑制时观察到的选择性聚腺苷化可能依赖于bud27。
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来源期刊
CiteScore
9.20
自引率
2.10%
发文量
63
审稿时长
44 days
期刊介绍: BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.
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