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Structures of the human spliceosomes before and after release of the ligated exon.

Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y
Cell Res 29 274-285 (2019)
Related entries: 6icz, 6id0

Cited: 45 times
EuropePMC logo PMID: 30728453

Abstract

Pre-mRNA splicing is executed by the spliceosome, which has eight major functional states each with distinct composition. Five of these eight human spliceosomal complexes, all preceding exon ligation, have been structurally characterized. In this study, we report the cryo-electron microscopy structures of the human post-catalytic spliceosome (P complex) and intron lariat spliceosome (ILS) at average resolutions of 3.0 and 2.9 Å, respectively. In the P complex, the ligated exon remains anchored to loop I of U5 small nuclear RNA, and the 3'-splice site is recognized by the junction between the 5'-splice site and the branch point sequence. The ATPase/helicase Prp22, along with the ligated exon and eight other proteins, are dissociated in the P-to-ILS transition. Intriguingly, the ILS complex exists in two distinct conformations, one with the ATPase/helicase Prp43 and one without. Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly.

Articles - 6id1 mentioned but not cited (3)

  1. Structures of the human spliceosomes before and after release of the ligated exon. Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, Shi Y. Cell Res. 29 274-285 (2019)
  2. A Snu114-GTP-Prp8 module forms a relay station for efficient splicing in yeast. Jia J, Ganichkin OM, Preußner M, Absmeier E, Alings C, Loll B, Heyd F, Wahl MC. Nucleic Acids Res. 48 4572-4584 (2020)
  3. research-article The debranching enzyme Dbr1 regulates lariat turnover and intron splicing. Buerer L, Clark N, Welch A, Duan C, Taggart A, Townley B, Wang J, Soemedi R, Rong S, Lin CL, Zeng Y, Katolik A, Staley J, Damha M, Mosammaparast N, Fairbrother W. Res Sq rs.3.rs-2931976 (2023)


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  4. A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing. Bergfort A, Preußner M, Kuropka B, Ilik İA, Hilal T, Weber G, Freund C, Aktaş T, Heyd F, Wahl MC. Nat Commun 13 1132 (2022)
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  19. Multi-omics data integration analysis identifies the spliceosome as a key regulator of DNA double-strand break repair. Sherill-Rofe D, Raban O, Findlay S, Rahat D, Unterman I, Samiei A, Yasmeen A, Kaiser Z, Kuasne H, Park M, Foulkes WD, Bloch I, Zick A, Gotlieb WH, Tabach Y, Orthwein A. NAR Cancer 4 zcac013 (2022)
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  23. Roles for the Synechococcus elongatus RNA-Binding Protein Rbp2 in Regulating the Circadian Clock. McKnight BM, Kang S, Le TH, Fang M, Carbonel G, Rodriguez E, Govindarajan S, Albocher-Kedem N, Tran AL, Duncan NR, Amster-Choder O, Golden SS, Cohen SE. J Biol Rhythms 38 447-460 (2023)
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  26. The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling. Bergfort A, Hilal T, Kuropka B, Ilik İA, Weber G, Aktaş T, Freund C, Wahl MC. Nucleic Acids Res 50 2938-2958 (2022)
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