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基因表达的RNA聚合酶II活性调控及其与疾病的关系

RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease.

作者信息

Kuldell James C, Kaplan Craig D

机构信息

Department of Biological Sciences, 202A LSA, Fifth and Ruskin Avenues, University of Pittsburgh, Pittsburgh PA 15260, United States.

Department of Biological Sciences, 202A LSA, Fifth and Ruskin Avenues, University of Pittsburgh, Pittsburgh PA 15260, United States.

出版信息

J Mol Biol. 2025 Jan 1;437(1):168770. doi: 10.1016/j.jmb.2024.168770. Epub 2024 Aug 28.

Abstract

Gene expression is dependent on RNA Polymerase II (Pol II) activity in eukaryotes. In addition to determining the rate of RNA synthesis for all protein coding genes, Pol II serves as a platform for the recruitment of factors and regulation of co-transcriptional events, from RNA processing to chromatin modification and remodeling. The transcriptome can be shaped by changes in Pol II kinetics affecting RNA synthesis itself or because of alterations to co-transcriptional events that are responsive to or coupled with transcription. Genetic, biochemical, and structural approaches to Pol II in model organisms have revealed critical insights into how Pol II works and the types of factors that regulate it. The complexity of Pol II regulation generally increases with organismal complexity. In this review, we describe fundamental aspects of how Pol II activity can shape gene expression, discuss recent advances in how Pol II elongation is regulated on genes, and how altered Pol II function is linked to human disease and aging.

摘要

在真核生物中,基因表达依赖于RNA聚合酶II(Pol II)的活性。除了决定所有蛋白质编码基因的RNA合成速率外,Pol II还作为一个平台,用于招募各种因子并调控共转录事件,从RNA加工到染色质修饰和重塑。转录组可以通过影响RNA合成本身的Pol II动力学变化来塑造,也可以由于对转录有反应或与转录偶联的共转录事件的改变而形成。在模式生物中对Pol II进行的遗传学、生物化学和结构研究方法,已经揭示了关于Pol II如何工作以及调控它的因子类型的关键见解。Pol II调控的复杂性通常随着生物复杂性的增加而增加。在这篇综述中,我们描述了Pol II活性如何塑造基因表达的基本方面,讨论了基因上Pol II延伸如何被调控以及Pol II功能改变如何与人类疾病和衰老相关联的最新进展。

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