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-Structure paper
タイトル | Mechanism for the initiation of spliceosome disassembly. |
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ジャーナル・号・ページ | Nature, Year 2024 |
掲載日 | 2024年6月26日 |
著者 | Matthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka / |
PubMed 要旨 | Pre-mRNA splicing requires the assembly, remodeling, and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly ...Pre-mRNA splicing requires the assembly, remodeling, and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodeling for catalysis, but the mechanism of disassembly remains unclear. Here, we report 2.6 to 3.2 Å resolution cryo-electron microscopy structures of nematode and human terminal intron-lariat spliceosomes along with biochemical and genetic data. Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly. The disassembly factors probe large inner and outer spliceosome surfaces to detect the release of ligated mRNA. Two of these factors, TFIP11 and C19L1, and three general spliceosome subunits, SYF1, SYF2 and SDE2, then dock and activate DHX15 on the catalytic U6 snRNA to initiate disassembly. U6 thus controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes. |
リンク | Nature / PubMed:38925148 |
手法 | EM (単粒子) |
解像度 | 2.73 - 69968.0 Å |
構造データ |
EMDB-50447: Structure of the C. elegans Intron Lariat Spliceosome (Map 1)
EMDB-50449: Structure of the C. elegans Intron Lariat Spliceosome (Map 2)
EMDB-50450: Structure of the C. elegans Intron Lariat Spliceosome (Map 3)
EMDB-50451: Structure of the C. elegans Intron Lariat Spliceosome (Map 4)
EMDB-50452: Structure of the C. elegans Intron Lariat Spliceosome (Map 5)
EMDB-50453: Structure of the C. elegans Intron Lariat Spliceosome (Map 6)
EMDB-50454: Structure of the C. elegans Intron Lariat Spliceosome (Map 7)
EMDB-50455: Structure of the C. elegans Intron Lariat Spliceosome (Map 8)
EMDB-50456: Structure of the C. elegans Intron Lariat Spliceosome (Map 9)
EMDB-50457: Structure of the C. elegans Intron Lariat Spliceosome (Map 10)
EMDB-50458: Structure of the C. elegans Intron Lariat Spliceosome (Map 11)
EMDB-50459: Structure of the C. elegans Intron Lariat Spliceosome (Map 12)
EMDB-50460: Structure of the C. elegans Intron Lariat Spliceosome (Map 13)
EMDB-50461: Structure of the C. elegans Intron Lariat Spliceosome (Map 14)
EMDB-50462: Structure of the C. elegans Intron Lariat Spliceosome (Map 15)
EMDB-50463: Structure of the C. elegans Intron Lariat Spliceosome (Map 16)
EMDB-50464: Structure of the C. elegans Intron Lariat Spliceosome (Map 17)
EMDB-50465: Structure of the C. elegans Intron Lariat Spliceosome (Map 18)
EMDB-50466: Structure of the C. elegans Intron Lariat Spliceosome (Map 19)
EMDB-50467: Structure of the C. elegans Intron Lariat Spliceosome (Map 20)
EMDB-50468: Structure of the C. elegans Intron Lariat Spliceosome (Map 21)
EMDB-50469: Structure of the C. elegans Intron Lariat Spliceosome (Map 22)
EMDB-50471: Structure of the C. elegans Intron Lariat Spliceosome (Map 23)
EMDB-50472: Structure of the C. elegans Intron Lariat Spliceosome (Map 24)
EMDB-50473: Structure of the C. elegans Intron Lariat Spliceosome (Map 25)
EMDB-50474: Structure of the C. elegans Intron Lariat Spliceosome (Map 27)
EMDB-50475: Structure of the C. elegans Intron Lariat Spliceosome (Map 26) PDB-9fmd: |
化合物 | ChemComp-MG: ChemComp-K: ChemComp-ATP: ChemComp-GTP: ChemComp-ZN: ChemComp-IHP: |
由来 |
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キーワード | SPLICING / P-complex / spliceosome |