西湖大学施一公教授和万蕊雪研究团队解析了人次要剪接体的活化态结构。2021年1月28日出版的《科学》发表了这项成果。

研究人员利用冷冻电镜解析了人次要剪接体激活态分辨率为2.9-Å的原子特征。U12型内含子的5'剪接位点和分支点序列分别被U6atac和U12小核仁RNA（snRNA）识别。五个新发现的蛋白质可稳定催化中心构象。锌指蛋白SCNM1模拟了主要剪接体SF3a复合体的功能。

RBM48/ARMC7复合物在U6atac snRNA的5'末端结合了γ-单甲基磷酸酯帽。U-box蛋白PPIL2协同调节U5 snRNA的环I，并使U5 snRNP稳定。CRIPT稳定了U12 snRNP。该研究为理解次要剪接体的功能提供了前提。

研究人员表示，次要剪接体介导了罕见但必需的U12型前体mRNA的剪接。

附：英文原文

Title: Structure of the activated human minor spliceosome

Author: Rui Bai, Ruixue Wan, Lin Wang, Kui Xu, Qiangfeng Zhang, Jianlin Lei, Yigong Shi

Issue&Volume: 2021/01/28

Abstract: The minor spliceosome mediates splicing of the rare but essential U12-type pre-mRNA. Here we report the atomic features of the activated human minor spliceosome determined by cryo-electron microscopy at 2.9- resolution. The 5′-splice site and branch point sequence of the U12-type intron are recognized by U6atac and U12 small nuclear RNA (snRNA), respectively. Five newly identified proteins stabilize the conformation of the catalytic center. The zinc finger protein SCNM1 functionally mimics the SF3a complex of the major spliceosome. The RBM48/ARMC7 complex binds the γ-monomethyl phosphate cap at the 5′-end of U6atac snRNA. The U-box protein PPIL2 coordinates loop I of U5 snRNA and stabilizes U5 snRNP. CRIPT stabilizes U12 snRNP. Our study provides a framework for mechanistic understanding of the function of the minor spliceosome.

DOI: 10.1126/science.abg0879

Source: https://science.sciencemag.org/content/early/2021/01/27/science.abg0879