Structure of the activated human minor spliceosome

Rui Bai; Ruixue Wan; Lin Wang; Kui Xu; Qiangfeng Zhang; Jianlin Lei; Yigong Shi

doi:10.1126/science.abg0879

Structure of the activated human minor spliceosome

Science. 2021 Mar 19;371(6535):eabg0879. doi: 10.1126/science.abg0879. Epub 2021 Jan 28.

Authors

Rui Bai^#^{1

2

3}, Ruixue Wan^#^{4

2

3}, Lin Wang⁵, Kui Xu⁵, Qiangfeng Zhang⁵, 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. wanruixue@westlake.edu.cn syg@westlake.edu.cn.
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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry
Adaptor Proteins, Signal Transducing / metabolism
Armadillo Domain Proteins / chemistry
Armadillo Domain Proteins / metabolism
Cryoelectron Microscopy
Cyclophilins / chemistry
Cyclophilins / metabolism
Humans
Introns
Models, Molecular
Nucleic Acid Conformation
Protein Conformation
Protein Domains
RNA Precursors / chemistry
RNA Precursors / metabolism
RNA Splicing
RNA Splicing Factors / chemistry
RNA Splicing Factors / metabolism
RNA, Small Nuclear / chemistry
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / metabolism
Ribonucleoprotein, U5 Small Nuclear / chemistry
Ribonucleoprotein, U5 Small Nuclear / metabolism
Ribonucleoproteins, Small Nuclear / metabolism
Spliceosomes / chemistry*
Spliceosomes / metabolism*

Substances

Adaptor Proteins, Signal Transducing
Armadillo Domain Proteins
CRIPT protein, human
RNA Precursors
RNA Splicing Factors
RNA, Small Nuclear
RNA-Binding Proteins
Ribonucleoprotein, U5 Small Nuclear
Ribonucleoproteins, Small Nuclear
SCNM1 protein, human
U11-U12 small nuclear ribonucleoprotein
Cyclophilins
PPIL2 protein, human