Structure of the activated human minor spliceosome.

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

Science (New York, N.Y.) 2021 Mar 19

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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. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Citation

Rui Bai, Ruixue Wan, Lin Wang, Kui Xu, Qiangfeng Zhang, Jianlin Lei, Yigong Shi. Structure of the activated human minor spliceosome. Science (New York, N.Y.). 2021 Mar 19;371(6535)