Structures and compositional dynamics of Mediator in transcription regulation

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Current opinion in structural biology Pub Date : 2024-07-26 DOI:10.1016/j.sbi.2024.102892

Tao Li, Ti-Chun Chao, Kuang-Lei Tsai

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Abstract

The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), functions as a critical coregulator during RNA polymerase II (RNAPII) transcription. cMED recruits RNAPII and facilitates the assembly of the pre-initiation complex (PIC) at promoters. In contrast, CKM prevents RNAPII binding to cMED while simultaneously exerting positive or negative influence on gene transcription through its kinase function. Recent structural studies on cMED and CKM have revealed their intricate architectures and subunit interactions. Here, we explore these structures, providing a comprehensive insight into Mediator (cMED-CKM) architecture and its potential mechanism in regulating RNAPII transcription. Additionally, we discuss the remaining puzzles that require further investigation to fully understand how cMED coordinates with CKM to regulate transcription in various events.

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转录调控中 Mediator 的结构和组成动态。

真核生物 Mediator 由一个大核心（cMED）和一个可分离的 CDK8 激酶模块（CKM）组成，在 RNA 聚合酶 II（RNAPII）转录过程中起着关键核心调节器的作用。相反，CKM 可阻止 RNAPII 与 cMED 结合，同时通过其激酶功能对基因转录产生积极或消极的影响。最近对 cMED 和 CKM 的结构研究揭示了它们错综复杂的结构和亚基相互作用。在此，我们将探讨这些结构，全面了解 Mediator（cMED-CKM）的结构及其调控 RNAPII 转录的潜在机制。此外，我们还讨论了仍需进一步研究的难题，以全面了解 cMED 如何与 CKM 相互协调，在各种事件中调控转录。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in structural biology 生物-生化与分子生物学

CiteScore

12.20

自引率

2.90%

发文量

179

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation

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