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动力学网络模型阐明 RNA 聚合酶 II 转录延伸的分子机制。

Molecular mechanisms of RNA polymerase II transcription elongation elucidated by kinetic network models.

机构信息

Bioengineering Graduate Program, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong; Center of Systems Biology and Human Health, State Key Laboratory of Molecular Neuroscience, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration & Reconstruction, Hong Kong.

Center of Systems Biology and Human Health, State Key Laboratory of Molecular Neuroscience, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration & Reconstruction, Hong Kong; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

出版信息

Curr Opin Struct Biol. 2018 Apr;49:54-62. doi: 10.1016/j.sbi.2018.01.002. Epub 2018 Feb 3.

Abstract

Transcription elongation cycle (TEC) of RNA polymerase II (Pol II) is a process of adding a nucleoside triphosphate to the growing messenger RNA chain. Due to the long timescale events in Pol II TEC, an advanced computational technique, such as Markov State Model (MSM), is needed to provide atomistic mechanism and reaction rates. The combination of MSM and experimental results can be used to build a kinetic network model (KNM) of the whole TEC. This review provides a brief protocol to build MSM and KNM of the whole TEC, along with the latest findings of MSM and other computational studies of Pol II TEC. Lastly, we offer a perspective on potentially using a sequence dependent KNM to predict genome-wide transcription error.

摘要

RNA 聚合酶 II(Pol II)的转录延伸循环(TEC)是向生长中的信使 RNA 链添加核苷三磷酸的过程。由于 Pol II TEC 中存在长时间尺度事件,因此需要使用先进的计算技术,如马尔可夫状态模型(MSM),以提供原子机制和反应速率。MSM 与实验结果的结合可用于构建整个 TEC 的动力学网络模型(KNM)。本综述提供了构建整个 TEC 的 MSM 和 KNM 的简要方案,以及 MSM 的最新发现和 Pol II TEC 的其他计算研究。最后,我们对使用基于序列的 KNM 来预测全基因组转录错误提供了一个视角。

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