小柯机器人

德国马克斯·普朗克生物物理化学研究所Patrick Cramer课题组揭示哺乳动物RNA聚合酶II起始前复合物的结构。该研究于2021年4月26日在线发表于国际一流学术期刊《自然》杂志上。

据研究人员介绍，转录的起始是在哺乳动物细胞分化和发育过程中调节基因活性的关键点。对于转录起始而言，RNA聚合酶II（Pol II）与通用转录因子组装成打开启动子DNA的起始前复合物（PIC）。先前的工作提供了酵母和人类PIC的分子结构，以及通过通用因子TFIIH打开DNA的拓扑模型。

研究人员报道了高分辨率的冷冻电镜PIC结构，其中包含了人类通用因子和家猪（Sus scrofa domesticus）Pol II，与人类Pol II的99.9％相同。研究人员以2.5–2.8Å的分辨率确定具有闭合和打开的启动子DNA的PIC结构，并以2.9–4.0Å的分辨率解析TFIIH。研究人员捕获了TFIIH易位酶XPB在易位前和易位后的状态，并表明XPB诱导并扩散DNA扭曲，从而启动TATA盒下游30个碱基对的DNA开放。研究人员还提供了证据，表明DNA开放分为两个步骤，并导致TFIIH从核心PIC脱离，这可能会阻止DNA扭曲并启用RNA链起始。 

附：英文原文

Title: Structures of mammalian RNA polymerase II pre-initiation complexes

Author: Shintaro Aibara, Sandra Schilbach, Patrick Cramer

Issue&Volume: 2021-04-26

Abstract: The initiation of transcription is a focal point for the regulation of gene activity during mammalian cell differentiation and development. For transcription initiation, RNA polymerase II (Pol II) assembles with general transcription factors into a pre-initiation complex (PIC) that opens promoter DNA. Previous work provided the molecular architecture of the yeast1–9 and human10,11 PIC and a topological model for DNA opening by the general factor TFIIH12–14. Here we report the high-resolution cryo-EM PIC structure comprising human general factors and Sus scrofa domesticus Pol II, which is 99.9% identical to human Pol II. We determine PIC structures with closed and opened promoter DNA at 2.5–2.8 resolution, and resolve TFIIH at 2.9–4.0 resolution. We capture the TFIIH translocase XPB in the pre- and post-translocation states and show that XPB induces and propagates a DNA twist to initiate DNA opening ~30 base pairs downstream of the TATA box. We also provide evidence that DNA opening occurs in two steps and leads to TFIIH detachment from the core PIC, which may stop DNA twisting and enable RNA chain initiation.

DOI: 10.1038/s41586-021-03554-8

Source: https://www.nature.com/articles/s41586-021-03554-8

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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