Structure of the activated human minor spliceosome

  • Science. 2021 Mar 19;371(6535):eabg0879. doi: 10.1126/science.abg0879.
Rui Bai  #  1  2  3 ,  Ruixue Wan  #  4  2  3 ,  Lin Wang  5 ,  Kui Xu  5 ,  Qiangfeng Zhang  5 ,  Jianlin Lei  5  6 ,  Yigong Shi  4  2  3  5
Affiliations
  • 1. Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Xihu District, Hangzhou 310024, Zhejiang Province, China.
  • 2. Westlake Laboratory of Life Sciences and Biomedicine, Xihu District, Hangzhou 310024, Zhejiang Province, China.
  • 3. Institute of Biology, Westlake Institute for Advanced Study, Xihu District, Hangzhou 310024, Zhejiang Province, China.
  • 4. Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Xihu District, Hangzhou 310024, Zhejiang Province, China. [email protected] [email protected].
  • 5. Beijing Advanced Innovation Center for Structural Biology and Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 6. Technology Center for Protein Sciences, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • # Contributed equally.
PMID: 33509932 DOI: 10.1126/science.abg0879
Abstract

The minor spliceosome mediates splicing of the rare but essential U12-type precursor messenger RNA. Here, we report the atomic features of the activated human minor spliceosome determined by cryo-electron microscopy at 2.9-angstrom resolution. The 5' splice site and branch point sequence of the U12-type intron are recognized by the U6atac and U12 small nuclear RNAs (snRNAs), 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 small nuclear ribonucleoprotein (snRNP), and CRIPT stabilizes U12 snRNP. Our study provides a framework for the mechanistic understanding of the function of the human minor spliceosome.