New insight into the biology of R-loops
New insight into the biology of R-loops
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DOI：
10.1016/j.mrfmmm.2020.111711
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发表时间：
2020-05-01
影响因子：
2.3
通讯作者：
Chakraborty, Prasun
中科院分区：
文献类型：
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作者：
Chakraborty, Prasun
当RNA与其模板DNA杂交，产生三链结构，留下错位的单链非模板DNA时，就会形成R环。在转录过程中，前进的RNA聚合酶后面的DNA负超螺旋将促进新生RNA形成R-环，因为DNA处于缠绕状态，以促进转录。在理论上，根据R环形成的背景，R环可分为病理性和非病理性两种。在基因调控和免疫球蛋白类转换区等各种生理活动中正常形成的R环被认为是非病理性的，而导致基因组不稳定的异常稳定的R环被认为是病理性的。虽然病理性R-环的形成是一种罕见的事件，但一旦形成，就会完全阻止转录、mRNA输出，增加突变，并抑制基因的表达。因此，R-环可以间接防止或诱导基因组不稳定，并且可能是DNA损伤的内源性来源。虽然R-环的存在早在几十年前就有报道，但由于试剂的存在，我们直到最近才了解到它在细胞中的形成和拆分。由于R-环连接了转录、mRNA剪接、DNA复制、重组和修复等重要的生物学过程，近年来引起了人们的极大兴趣。在这篇综述中，我将重点介绍R-环的形成和分解的最新进展，基于现有的方法，利用生化、细胞生物学和分子生物学的方法来研究R-环。
R-loops form when RNA hybridizes with its template DNA generating a three-stranded structure leaving a dis-placed single strand non-template DNA. During transcription negative supercoiling of DNA behind the advancing RNA polymerase will facilitate the formation of R-loops by the nascent RNA as the DNA is under wound to facilitate transcription. In theory R-loops are classified into pathological and non-pathological depending on the context of its formation. R-loop which are formed normally in various physiological events like in gene regulation and at immunoglobulin class switch regions are considered non-pathological, whereas abnormally stable R-loop which leads to genomic instability are considered pathological. Although pathological R-loop formation is a rare event but once formed completely blocks transcription, mRNA export, elevates mutagenesis, and inhibits gene expression. Hence, R-loop either prevents or induces genomic instability indirectly and are potentially an endogenous source of DNA lesion. Although the existence of R-loop has been reported few decades ago, but only recently we have gained knowledge about its formation and resolution in cells due to the availability of reagents. R-loop biology has generated immense interest in past few years since it connects the important biological processes such as transcription, mRNA splicing, DNA replication, recombination and repair. In this review I will focus on the recent progress made about formation and resolution of R-loop, based on the methodologies that are currently available to study R-loop using biochemical, cell biology and molecular biology approaches.