核核糖核蛋白家族成员FUS与RNA的结合可以阻断R环形RNA：DNA杂交结构的形成。
Binding of the nuclear ribonucleoprotein family member FUS to RNA prevents R-loop RNA:DNA hybrid structures.
发表日期：2023 Sep 08
作者：
Valery F Thompson, Daniel R Wieland, Vivian Mendoza-Leon, Helen I Janis, Michelle A Lay, Lucas M Harrell, Jacob C Schwartz
来源：
Cellular & Molecular Immunology
摘要：
融合在肉瘤中的蛋白（FUS，FUSed in sarcoma）是一种影响所有三种核聚合酶产生的有丝分裂动物的RNA结合蛋白。FUS还结合着新生转录本、RNA处理因子、RNA聚合酶和转录机器。在这里，我们探索了FUS结合相互作用在转录过程中的作用。体外流出转录实验显示FUS提高了非真核生物聚合酶产生的RNA。活性还减少了RNA产物与其DNA模板之间的R-loop形成。通过领域突变和删除的分析表明，RNA结合对活性是必需的。我们解释道，FUS结合并隔离新生转录本以防止其与附近DNA形成R-loop。DRIP-seq分析显示，FUS的沉默增加了表达基因附近R-loop的富集。FUS通过结合新生转录本来预防R-loop有可能影响任何RNA聚合酶的转录，突显了FUS对细胞和疾病中RNA代谢的广泛影响。
版权所有©2023 Elsevier Inc.。由The Authors发布。保留所有权利。
The protein FUS (FUSed in sarcoma) is a metazoan RNA-binding protein that influences RNA production by all three nuclear polymerases. FUS also binds nascent transcripts, RNA processing factors, RNA polymerases, and transcription machinery. Here, we explored the role of FUS binding interactions for activity during transcription. In vitro run-off transcription assays revealed FUS enhanced RNA produced by a non-eukaryote polymerase. Activity also reduced the formation of R-loops between RNA products and their DNA template. Analysis by domain mutation and deletion indicated RNA-binding was required for activity. We interpret that FUS binds and sequesters nascent transcripts to prevent R-loops forming with nearby DNA. DRIP-seq analysis showed that a knockdown of FUS increased R-loop enrichment near expressed genes. Prevention of R-loops by FUS binding to nascent transcripts has potential to affect transcription by any RNA polymerase, highlighting the broad impact FUS can have on RNA metabolism in cells and disease.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.