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Nuclear compartmentalization as a mechanism of quantitative control of gene expression
Nature Reviews Molecular Cell Biology ( IF 81.3 ) Pub Date : 2021-08-02 , DOI: 10.1038/s41580-021-00387-1
Prashant Bhat 1, 2 , Drew Honson 1 , Mitchell Guttman 1
Affiliation  

Gene regulation requires the dynamic coordination of hundreds of regulatory factors at precise genomic and RNA targets. Although many regulatory factors have specific affinity for their nucleic acid targets, molecular diffusion and affinity models alone cannot explain many of the quantitative features of gene regulation in the nucleus. One emerging explanation for these quantitative properties is that DNA, RNA and proteins organize within precise, 3D compartments in the nucleus to concentrate groups of functionally related molecules. Recently, nucleic acids and proteins involved in many important nuclear processes have been shown to engage in cooperative interactions, which lead to the formation of condensates that partition the nucleus. In this Review, we discuss an emerging perspective of gene regulation, which moves away from classic models of stoichiometric interactions towards an understanding of how spatial compartmentalization can lead to non-stoichiometric molecular interactions and non-linear regulatory behaviours. We describe key mechanisms of nuclear compartment formation, including emerging roles for non-coding RNAs in facilitating their formation, and discuss the functional role of nuclear compartments in transcription regulation, co-transcriptional and post-transcriptional RNA processing, and higher-order chromatin regulation. More generally, we discuss how compartmentalization may explain important quantitative aspects of gene regulation.



中文翻译:

核区室化作为基因表达定量控制的机制

基因调控需要在精确的基因组和 RNA 目标上动态协调数百个调控因子。尽管许多调节因子对其核酸靶标具有特定的亲和力,但仅靠分子扩散和亲和力模型并不能解释细胞核中基因调控的许多定量特征。对这些定量特性的一种新解释是,DNA、RNA 和蛋白质在细胞核中精确的 3D 隔室中组织起来,以集中功能相关的分子组。最近,参与许多重要核过程的核酸和蛋白质已被证明参与协同相互作用,从而导致形成分隔核的凝聚物。在这篇综述中,我们讨论了基因调控的一个新兴观点,它从化学计量相互作用的经典模型转向了解空间划分如何导致非化学计量分子相互作用和非线性调节行为。我们描述了核区室形成的关键机制,包括非编码 RNA 在促进其形成中的新作用,并讨论了核区室在转录调控、共转录和转录后 RNA 加工以及高阶染色质调控中的功能作用. 更一般地说,我们讨论区室化如何解释基因调控的重要定量方面。我们描述了核区室形成的关键机制,包括非编码 RNA 在促进其形成中的新作用,并讨论了核区室在转录调控、共转录和转录后 RNA 加工以及高阶染色质调控中的功能作用. 更一般地说,我们讨论区室化如何解释基因调控的重要定量方面。我们描述了核区室形成的关键机制,包括非编码 RNA 在促进其形成中的新作用,并讨论了核区室在转录调控、共转录和转录后 RNA 加工以及高阶染色质调控中的功能作用. 更一般地说,我们讨论区室化如何解释基因调控的重要定量方面。

更新日期:2021-08-02
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