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转录 RNA 聚合酶:双超螺旋域的动力学。

Transcribing RNA polymerases: Dynamics of twin supercoiled domains.

机构信息

Laboratoire Interdisciplinaire de Physique, CNRS and Université Grenoble Alpes, St Martin d'Hères, France.

出版信息

Biophys J. 2024 Nov 19;123(22):3898-3910. doi: 10.1016/j.bpj.2024.10.002. Epub 2024 Oct 4.

Abstract

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.

摘要

RNA 聚合酶(RNAP)酶的基因转录需要双链 DNA 局部和瞬时打开,这导致 RNAP 下游的 DNA 超螺旋增加,上游的超螺旋减少。当 DNA 最初扭转松弛并且 RNAP 经历足够大的旋转阻力时,这些变化导致在 RNAP 前方形成正超螺旋扭结,在其后方形成负超螺旋扭结,这一特征称为“双超螺旋域”(TSD)。这项工作旨在更详细地破译由 RNAP 酶转录的环状 DNA 分子的扭转动力学。为此,我们使用专门设计的粗粒模型进行了布朗动力学模拟。根据 DNA 分子的超螺旋密度和 RNAP 的扭转注入率与旋转松弛速度的比值,模拟揭示了丰富的行为面板,这些行为有时与粗略的 TSD 图像明显不同。特别是,对于足够慢的旋转松弛速度,正超螺旋扭结永远不会在转录具有生理负超螺旋的 DNA 分子的 RNAP 前方形成。相反,负超螺旋扭结几乎周期性地在 RNAP 的上游侧形成,并在从 RNAP 脱离并迅速失稳之前增长到一定长度。还讨论了拓扑障碍阻碍 TSD 动力学的程度。

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