Structural basis of exoribonuclease-mediated mRNA transcription termination

• 成果类型: Article
• 署名作者: Zeng, Yuan; Zhang, Hong-Wei; Wu, Xiao-Xian; Zhang, Yu
• 署名单位: Chinese Academy of Sciences; Center for Excellence in Molecular Plant Sciences, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6857
• DOI: 10.1038/s41586-024-07240-3
• 发表日期: 2024-04-25
• 页码: 887-+
• 关键词: polymerase-ii termination; premature termination; elongation complex; poly(a) signal; protein; transitions; purification; mechanism; cleavage; reveals

摘要

Efficient termination is required for robust gene transcription. Eukaryotic organisms use a conserved exoribonuclease-mediated mechanism to terminate the mRNA transcription by RNA polymerase II (Pol II)(1-5). 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.