How Is Precursor Messenger RNA Spliced by the Spliceosome?
- PMID:31815536
- DOI: 10.1146/annurev-biochem-013118-111024
How Is Precursor Messenger RNA Spliced by the Spliceosome?
Abstract
Splicing of the precursor messenger RNA, involving intron removal and exon ligation, is mediated by the spliceosome. Together with biochemical and genetic investigations of the past four decades, structural studies of the intact spliceosome at atomic resolution since 2015 have led to mechanistic delineation of RNA splicing with remarkable insights. The spliceosome is proven to be a protein-orchestrated metalloribozyme. Conserved elements of small nuclear RNA (snRNA) constitute the splicing active site with two catalytic metal ions and recognize three conserved intron elements through duplex formation, which are delivered into the splicing active site for branching and exon ligation. The protein components of the spliceosome stabilize the conformation of the snRNA, drive spliceosome remodeling, orchestrate the movement of the RNA elements, and facilitate the splicing reaction. The overall organization of the spliceosome and the configuration of the splicing active site are strictly conserved between human and yeast.
Keywords: branching; exon ligation; pre-mRNA splicing; small nuclear RNA; small nuclear ribonuclear protein; snRNA; snRNP; spliceosome.
Similar articles
- RNA Splicing by the Spliceosome.Wilkinson ME, Charenton C, Nagai K.Wilkinson ME, et al.Annu Rev Biochem. 2020 Jun 20;89:359-388. doi: 10.1146/annurev-biochem-091719-064225. Epub 2019 Dec 3.Annu Rev Biochem. 2020.PMID:31794245Review.
- Structure of a pre-catalytic spliceosome.Plaschka C, Lin PC, Nagai K.Plaschka C, et al.Nature. 2017 Jun 29;546(7660):617-621. doi: 10.1038/nature22799. Epub 2017 May 22.Nature. 2017.PMID:28530653Free PMC article.
- Cryo-EM structure of the spliceosome immediately after branching.Galej WP, Wilkinson ME, Fica SM, Oubridge C, Newman AJ, Nagai K.Galej WP, et al.Nature. 2016 Sep 8;537(7619):197-201. doi: 10.1038/nature19316. Epub 2016 Jul 26.Nature. 2016.PMID:27459055Free PMC article.
- Cwc21p promotes the second step conformation of the spliceosome and modulates 3' splice site selection.Gautam A, Grainger RJ, Vilardell J, Barrass JD, Beggs JD.Gautam A, et al.Nucleic Acids Res. 2015 Mar 31;43(6):3309-17. doi: 10.1093/nar/gkv159. Epub 2015 Mar 3.Nucleic Acids Res. 2015.PMID:25740649Free PMC article.
- Structural dynamics of the N-terminal domain and the Switch loop of Prp8 during spliceosome assembly and activation.Jia X, Sun C.Jia X, et al.Nucleic Acids Res. 2018 May 4;46(8):3833-3840. doi: 10.1093/nar/gky242.Nucleic Acids Res. 2018.PMID:29635373Free PMC article.Review.
Cited by
- Mechanism for the initiation of spliceosome disassembly.Vorländer MK, Rothe P, Kleifeld J, Cormack ED, Veleti L, Riabov-Bassat D, Fin L, Phillips AW, Cochella L, Plaschka C.Vorländer MK, et al.Nature. 2024 Aug;632(8024):443-450. doi: 10.1038/s41586-024-07741-1. Epub 2024 Jun 26.Nature. 2024.PMID:38925148Free PMC article.
- The rice blast fungus SR protein 1 regulates alternative splicing with unique mechanisms.Shi W, Yang J, Chen D, Yin C, Zhang H, Xu X, Pan X, Wang R, Fei L, Li M, Qi L, Bhadauria V, Liu J, Peng YL.Shi W, et al.PLoS Pathog. 2022 Dec 8;18(12):e1011036. doi: 10.1371/journal.ppat.1011036. eCollection 2022 Dec.PLoS Pathog. 2022.PMID:36480554Free PMC article.
- RNA exon editing: Splicing the way to treat human diseases.Doi A, Delaney C, Tanner D, Burkhart K, Bell RD.Doi A, et al.Mol Ther Nucleic Acids. 2024 Aug 16;35(3):102311. doi: 10.1016/j.omtn.2024.102311. eCollection 2024 Sep 10.Mol Ther Nucleic Acids. 2024.PMID:39281698Free PMC article.Review.
- Beyond Back Splicing, a Still Poorly Explored World: Non-Canonical Circular RNAs.Robic A, Kühn C.Robic A, et al.Genes (Basel). 2020 Sep 22;11(9):1111. doi: 10.3390/genes11091111.Genes (Basel). 2020.PMID:32972011Free PMC article.Review.
- CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 is an RNA-binding protein controlling plant immunity via an RNA processing complex.Peng S, Guo D, Guo Y, Zhao H, Mei J, Han Y, Guan R, Wang T, Song T, Sun K, Liu Y, Mao T, Chang H, Xue J, Cai Y, Chen D, Wang S.Peng S, et al.Plant Cell. 2022 Apr 26;34(5):1724-1744. doi: 10.1093/plcell/koac037.Plant Cell. 2022.PMID:35137215Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous