中国科学院分子植物科学卓越创新中心张余团队揭示核糖核酸外切酶介导mRNA转录终止的结构基础。相关论文于2024年3月27日在线发表在《自然》杂志上。

研究人员报告了两种冷冻电镜结构，它们是与5′-to-3′核糖核酸外切酶Rat1及其伙伴Rai1结合的酿酒酵母RNA聚合酶II（Pol II）预终止转录复合物。结构显示，Rat1取代了延伸因子Spt5，使其与Pol II柄结构域对接。Rat1保护Pol II的RNA出口通道，引导新生RNA向其活性中心移动，并在新生RNA的5′末端堆叠三个核苷酸。

这些结构进一步表明，Rat1在缩短RNA时会向Pol II旋转。这些研究结果为酵母中Pol II介导的Rat1终止mRNA转录以及其他真核生物中核糖核酸外切酶介导的mRNA转录终止提供了结构机制。。

据介绍，高效的终止是基因稳健转录的必要条件。真核生物使用一种保守的核糖核酸外切酶介导机制来终止Pol II的mRNA转录。

附：英文原文

Title: Structural basis of exoribonuclease-mediated mRNA transcription termination

Author: Zeng, Yuan, Zhang, Hong-Wei, Wu, Xiao-Xian, Zhang, Yu

Issue&Volume: 2024-03-27

Abstract: Efficient termination is required for robust gene transcription. Eukaryotic organisms use a conserved exoribonuclease-mediated mechanism to terminate the mRNA transcription by RNA polymeraseII (Pol II)1,2,3,4,5. Here we report two cryogenic electron microscopy structures of Saccharomyces cerevisiae Pol II pre-termination transcription complexes bound to the 5′-to-3′ exoribonuclease Rat1 and its partner Rai1. Our structures show that Rat1 displaces the elongation factor Spt5 to dock at the Pol II stalk domain. Rat1 shields the RNA exit channel of Pol II, guides the nascent RNA towards its active centre and stacks three nucleotides at the 5′terminus of the nascent RNA. The structures further show that Rat1 rotates towards Pol II as it shortens RNA. Our results provide the structural mechanism for the Rat1-mediated termination of mRNA transcription by Pol II in yeast and the exoribonuclease-mediated termination of mRNA transcription in other eukaryotes.

DOI: 10.1038/s41586-024-07240-3

Source: https://www.nature.com/articles/s41586-024-07240-3