复旦大学徐彦辉研究团队揭示转录起始复合物的组装机制。相关论文于2021年4月1日在线发表在《科学》杂志上。

据研究人员介绍，转录因子IID（TFIID）识别核心启动子并支持RNA聚合酶（Pol）II介导的真核转录的预启动复合物（PIC）组装。

研究人员确定了基于人类TFIID的PIC在三个逐步组装状态下的结构，并揭示了两个途径的PIC组装：在途径I上（在TATA-DBE启动子上），与靠近Pol II的启动子进行逐步聚集，然后实现广泛的模块重组；在途径II上（在仅TATA和无TATA的启动子上），直接在启动子处聚集。 这两条轨道以相同的构象收敛在50个亚基的完整PIC上，从而TFIID稳定了PIC的组织，并支持在Pol II和CAK介导的Pol II C末端结构域上加载（CDK）激活激酶（CAK）。

出乎意料的是，TFIID的TBP类似地弯曲了PIC中的TATA框和无TATA的启动子。这项研究可视化了高度多样化的启动子上的PIC逐步组装。 

附：英文原文

Title: Structural insights into preinitiation complex assembly on core promoters

Author: Xizi Chen, Yilun Qi, Zihan Wu, Xinxin Wang, Jiabei Li, Dan Zhao, Haifeng Hou, Yan Li, Zishuo Yu, Weida Liu, Mo Wang, Yulei Ren, Ze Li, Huirong Yang, Yanhui Xu

Issue&Volume: 2021/04/01

Abstract: Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase (Pol) II-mediated eukaryotic transcription. Here, we determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-DBE promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at ~50-subunit holo-PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of Pol II C-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.

DOI: 10.1126/science.aba8490

Source: https://science.sciencemag.org/content/early/2021/03/31/science.aba8490