Structure of the activated human minor spliceosome

• Published in: Science (American Association for the Advancement of Science) 2021-03, Vol.371 (6535)
• Main Authors: Bai, Rui, Wan, Ruixue, Wang, Lin, Xu, Kui, Zhang, Qiangfeng, Lei, Jianlin, Shi, Yigong
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - metabolism; Adenosine triphosphatase; Armadillo Domain Proteins - chemistry; Armadillo Domain Proteins - metabolism; Assembly; Atomic structure; Binding sites; Catalysis; Coding; Cryoelectron Microscopy; Cyclophilins - chemistry; Cyclophilins - metabolism; DNA helicase; Domains; Electron microscopy; Exons; Gene mapping; Genomes; Guanine; Heavy metals; Homology; Humans; Inserts; Introns; Microscopy; Models, Molecular; mRNA; Nucleic Acid Conformation; Nucleotides; Precursors; Protein Conformation; Protein Domains; Protein purification; Proteins; Purification; Regulatory mechanisms (biology); Ribonucleic acid; Ribonucleoprotein, U5 Small Nuclear - chemistry; Ribonucleoprotein, U5 Small Nuclear - metabolism; Ribonucleoproteins (small nuclear); Ribonucleoproteins (U2 small nuclear); Ribonucleoproteins, Small Nuclear - metabolism; RNA; 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; snRNA; Spliceosomes; Spliceosomes - chemistry; Spliceosomes - metabolism; Splicing; Splicing factors; Transmission electron microscopy; Zinc finger proteins
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abg0879

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.