{"title":"转录 RNA 聚合酶:双超卷曲域的动力学。","authors":"Marc Joyeux","doi":"10.1016/j.bpj.2024.10.002","DOIUrl":null,"url":null,"abstract":"<p><p>Gene transcription by an RNA polymerase (RNAP) enzyme requires that double-stranded DNA be locally and transiently opened, which results in an increase of DNA supercoiling downstream of the RNAP and a decrease of supercoiling upstream of it. When the DNA is initially torsionally relaxed and the RNAP experiences sufficiently large rotational drag, these variations lead to positively supercoiled plectonemes ahead of the RNAPs and negatively supercoiled ones behind it, a feature known as \"twin supercoiled domain\" (TSD). This work aims at deciphering into some more detail the torsional dynamics of circular DNA molecules being transcribed by RNAP enzymes. To this end, we performed Brownian dynamics simulations with a specially designed coarse-grained model. Depending on the superhelical density of the DNA molecule and the ratio of RNAP's twist injection rate and rotational relaxation speed, simulations reveal a rich panel of behaviors, which sometimes differ markedly from the crude TSD picture. In particular, for sufficiently slow rotational relaxation speed, positively supercoiled plectonemes never form ahead of an RNAP that transcribes a DNA molecule with physiological negative supercoiling. Rather, negatively supercoiled plectonemes form almost periodically at the upstream side of the RNAP and grow up to a certain length before detaching from the RNAP and destabilizing rapidly. The extent to which topological barriers hinder the dynamics of TSDs is also discussed.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"3898-3910"},"PeriodicalIF":3.2000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transcribing RNA polymerases: Dynamics of twin supercoiled domains.\",\"authors\":\"Marc Joyeux\",\"doi\":\"10.1016/j.bpj.2024.10.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gene transcription by an RNA polymerase (RNAP) enzyme requires that double-stranded DNA be locally and transiently opened, which results in an increase of DNA supercoiling downstream of the RNAP and a decrease of supercoiling upstream of it. When the DNA is initially torsionally relaxed and the RNAP experiences sufficiently large rotational drag, these variations lead to positively supercoiled plectonemes ahead of the RNAPs and negatively supercoiled ones behind it, a feature known as \\\"twin supercoiled domain\\\" (TSD). This work aims at deciphering into some more detail the torsional dynamics of circular DNA molecules being transcribed by RNAP enzymes. To this end, we performed Brownian dynamics simulations with a specially designed coarse-grained model. Depending on the superhelical density of the DNA molecule and the ratio of RNAP's twist injection rate and rotational relaxation speed, simulations reveal a rich panel of behaviors, which sometimes differ markedly from the crude TSD picture. In particular, for sufficiently slow rotational relaxation speed, positively supercoiled plectonemes never form ahead of an RNAP that transcribes a DNA molecule with physiological negative supercoiling. Rather, negatively supercoiled plectonemes form almost periodically at the upstream side of the RNAP and grow up to a certain length before detaching from the RNAP and destabilizing rapidly. The extent to which topological barriers hinder the dynamics of TSDs is also discussed.</p>\",\"PeriodicalId\":8922,\"journal\":{\"name\":\"Biophysical journal\",\"volume\":\" \",\"pages\":\"3898-3910\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biophysical journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bpj.2024.10.002\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysical journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.bpj.2024.10.002","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/4 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0
摘要
RNA 聚合酶(RNAP)的基因转录要求双链 DNA 在局部瞬时打开,这导致 RNAP 下游的 DNA 超卷曲增加,上游的超卷曲减少。当DNA最初扭转松弛,RNAP受到足够大的旋转阻力时,这些变化会导致RNAP前方出现正向超卷曲纠缠,后方出现负向超卷曲纠缠,这一特征被称为 "双超卷曲域"(TSD)。本研究旨在更详细地解读 RNAP 酶转录环状 DNA 分子的扭转动力学。为此,我们使用专门设计的粗粒度模型进行了布朗动力学模拟。根据 DNA 分子的超螺旋密度以及 RNAP 扭转注入率和旋转松弛速度的比率,模拟结果显示了丰富的行为,这些行为有时与粗略的 TSD 图像明显不同。特别是,在旋转松弛速度足够慢的情况下,在转录具有生理性负超卷曲的 DNA 分子的 RNAP 之前,绝不会形成正超卷曲的纠缠因子。相反,在 RNAP 的上游一侧几乎周期性地形成负超卷偏导线,并在长到一定长度后脱离 RNAP 并迅速失去稳定。此外,还讨论了拓扑障碍在多大程度上阻碍了 TSD 的动态变化。
Transcribing RNA polymerases: Dynamics of twin supercoiled domains.
Gene transcription by an RNA polymerase (RNAP) enzyme requires that double-stranded DNA be locally and transiently opened, which results in an increase of DNA supercoiling downstream of the RNAP and a decrease of supercoiling upstream of it. When the DNA is initially torsionally relaxed and the RNAP experiences sufficiently large rotational drag, these variations lead to positively supercoiled plectonemes ahead of the RNAPs and negatively supercoiled ones behind it, a feature known as "twin supercoiled domain" (TSD). This work aims at deciphering into some more detail the torsional dynamics of circular DNA molecules being transcribed by RNAP enzymes. To this end, we performed Brownian dynamics simulations with a specially designed coarse-grained model. Depending on the superhelical density of the DNA molecule and the ratio of RNAP's twist injection rate and rotational relaxation speed, simulations reveal a rich panel of behaviors, which sometimes differ markedly from the crude TSD picture. In particular, for sufficiently slow rotational relaxation speed, positively supercoiled plectonemes never form ahead of an RNAP that transcribes a DNA molecule with physiological negative supercoiling. Rather, negatively supercoiled plectonemes form almost periodically at the upstream side of the RNAP and grow up to a certain length before detaching from the RNAP and destabilizing rapidly. The extent to which topological barriers hinder the dynamics of TSDs is also discussed.
期刊介绍:
BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.