转录起始前复合物组装的结构见解。

Structural insights into assembly of transcription preinitiation complex.

机构信息

Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Department of Biochemistry and Biophysics, School of Life Sciences, Shanghai Key Laboratory of Radiation Oncology, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China; The International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, China; Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China; Human Phenome Institute, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.

出版信息

Curr Opin Struct Biol. 2022 Aug;75:102404. doi: 10.1016/j.sbi.2022.102404. Epub 2022 Jun 11.

DOI:10.1016/j.sbi.2022.102404

PMID:35700575

Abstract

RNA polymerase II (Pol II)-mediated transcription in eukaryotic cells starts with assembly of preinitiation complex (PIC) on core promoter, a DNA sequence of ∼100 base pairs. The transcription PIC consists of Pol II and general transcription factors TFIID, TFIIA, TFIIB, TFIIF, TFIIE, and TFIIH. Previous structural studies focused on PIC assembled on TATA box promoters with TFIID replaced by its subunit, TATA box-binding protein (TBP). However, the megadalton TFIID complex is essential for promoter recognition, TBP loading onto promoter, and PIC assembly for almost all Pol II-mediated transcription, especially on the TATA-less promoters, which account for ∼85% of core promoters of human coding genes. The functions of TFIID could not be replaced by TBP. The recent breakthrough in structure determination of TFIID-based PIC complexes in different assembly stages revealed mechanistic insights into PIC assembly on TATA box and TATA-less promotes and provided a framework for further investigation of transcription initiation.

摘要

真核细胞中的 RNA 聚合酶 II（Pol II）介导的转录起始于核心启动子上预起始复合物（PIC）的组装，核心启动子是一个约 100 个碱基对的 DNA 序列。转录 PIC 由 Pol II 和通用转录因子 TFIID、TFIIA、TFIIB、TFIIF、TFIIE 和 TFIIH 组成。以前的结构研究主要集中在 TATA 盒启动子上组装的 PIC，其中 TFIID 被其亚基 TATA 盒结合蛋白（TBP）取代。然而，兆道尔顿 TFIID 复合物对于启动子识别、TBP 加载到启动子上以及 PIC 组装对于几乎所有由 Pol II 介导的转录都是必不可少的，特别是在 TATA 缺失的启动子上，这些启动子占人类编码基因核心启动子的约 85%。TFIID 的功能不能被 TBP 取代。最近在不同组装阶段确定基于 TFIID 的 PIC 复合物的结构方面取得了突破，揭示了 PIC 在 TATA 盒和 TATA 缺失启动子上组装的机制见解，并为进一步研究转录起始提供了框架。