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R 环形成的拓扑结构和动力学。

Topology and kinetics of R-loop formation.

机构信息

39152 Guardino Dr., apt 201, Fremont, California.

Department of Biology, Stanford University, Stanford, California.

出版信息

Biophys J. 2022 Sep 20;121(18):3345-3357. doi: 10.1016/j.bpj.2022.08.026. Epub 2022 Aug 24.

Abstract

R-loops are structures containing an RNA-DNA duplex and an unpaired DNA strand. They can be formed upon "invasion" of an RNA strand into a DNA duplex, during which the RNA displaces the homologous DNA strand and binds the complementary strand. R-loops have many significant beneficial or deleterious biological effects, so it is important to understand the mechanisms for their generation and processing. We propose a model for co-transcriptional R-loop formation, in which their generation requires passage of the nascent RNA "tail" through the gap between the separated DNA strands. This passage becomes increasingly difficult with lengthening of the RNA tail. The length of the tail increases upon increasing distance between the transcription start site and the site of R-loop initiation. This causes reduced yields of R-loops with greater distance from the transcription start site. However, alternative pathways for R-loop formation are possible, involving either transient disruption of the transcription complex or the hypothetical formation of a triple-stranded structure, as a "collapsed R-loop." These alternative pathways could account for the fact that in many systems R-loops are observed very far from the transcription start site. Our model is consistent with experimental data and makes general predictions about the kinetics of R-loop formation.

摘要

R 环是含有 RNA-DNA 双链和一条未配对 DNA 链的结构。它们可以在 RNA 链“入侵”DNA 双链时形成,在此过程中,RNA 取代同源 DNA 链并与互补链结合。R 环具有许多重要的有益或有害的生物学效应,因此了解其生成和处理的机制非常重要。我们提出了一个共转录 R 环形成的模型,其中它们的生成需要新生 RNA“尾巴”通过分离的 DNA 链之间的间隙。随着 RNA 尾巴的延长,这种通过变得越来越困难。随着转录起始位点和 R 环起始位点之间距离的增加,尾巴的长度增加。这导致与转录起始位点的距离越大,R 环的产量越低。然而,R 环形成的替代途径是可能的,涉及转录复合物的瞬时中断或假设形成三链结构,作为“折叠的 R 环”。这些替代途径可以解释为什么在许多系统中,R 环都在远离转录起始位点的地方被观察到。我们的模型与实验数据一致,并对 R 环形成的动力学做出了一般性预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c8/9515371/c9220cd76706/fx1.jpg

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