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Structure paper

TitleMechanism for the initiation of spliceosome disassembly.
Journal, issue, pagesNature, Vol. 632, Issue 8024, Page 443-450, Year 2024
Publish dateJun 26, 2024
AuthorsMatthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric D Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka /
PubMed AbstractPrecursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on ...Precursor-mRNA (pre-mRNA) splicing requires the assembly, remodelling and disassembly of the multi-megadalton ribonucleoprotein complex called the spliceosome. Recent studies have shed light on spliceosome assembly and remodelling for catalysis, but the mechanism of disassembly remains unclear. Here we report 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 therefore controls both the start and end of pre-mRNA splicing. Taken together, our results explain the molecular basis of the initiation of canonical spliceosome disassembly and provide a framework to understand general spliceosomal RNA helicase control and the discard of aberrant spliceosomes.
External linksNature / PubMed:38925148 / PubMed Central
MethodsEM (single particle)
Resolution2.73 - 69968.0 Å
Structure data

EMDB-19397: Composite map of the C. elegans Intron Lariat Spliceosome primed for disassembly (ILS')
PDB-8ro0: Structure of the C. elegans Intron Lariat Spliceosome primed for disassembly (ILS')
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-19398, PDB-8ro1:
Structure of the C. elegans Intron Lariat Spliceosome double-primed for disassembly (ILS'')
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-19399, PDB-8ro2:
Integrative Structure of the human intron lariat Spliceosome (ILS'')
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-50447: Structure of the C. elegans Intron Lariat Spliceosome (Map 1)
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-50449: Structure of the C. elegans Intron Lariat Spliceosome (Map 2)
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-50450: Structure of the C. elegans Intron Lariat Spliceosome (Map 3)
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-50451: Structure of the C. elegans Intron Lariat Spliceosome (Map 4)
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-50452: Structure of the C. elegans Intron Lariat Spliceosome (Map 5)
Method: EM (single particle) / Resolution: 5.51 Å

EMDB-50453: Structure of the C. elegans Intron Lariat Spliceosome (Map 6)
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-50454: Structure of the C. elegans Intron Lariat Spliceosome (Map 7)
Method: EM (single particle) / Resolution: 6.35 Å

EMDB-50455: Structure of the C. elegans Intron Lariat Spliceosome (Map 8)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-50456: Structure of the C. elegans Intron Lariat Spliceosome (Map 9)
Method: EM (single particle) / Resolution: 3.69 Å

EMDB-50457: Structure of the C. elegans Intron Lariat Spliceosome (Map 10)
Method: EM (single particle) / Resolution: 2.73 Å

EMDB-50458: Structure of the C. elegans Intron Lariat Spliceosome (Map 11)
Method: EM (single particle) / Resolution: 3.03 Å

EMDB-50459: Structure of the C. elegans Intron Lariat Spliceosome (Map 12)
Method: EM (single particle) / Resolution: 4.77 Å

EMDB-50460: Structure of the C. elegans Intron Lariat Spliceosome (Map 13)
Method: EM (single particle) / Resolution: 6.4 Å

EMDB-50461: Structure of the C. elegans Intron Lariat Spliceosome (Map 14)
Method: EM (single particle) / Resolution: 4.24 Å

EMDB-50462: Structure of the C. elegans Intron Lariat Spliceosome (Map 15)
Method: EM (single particle) / Resolution: 3.61 Å

EMDB-50463: Structure of the C. elegans Intron Lariat Spliceosome (Map 16)
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-50464: Structure of the C. elegans Intron Lariat Spliceosome (Map 17)
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-50465: Structure of the C. elegans Intron Lariat Spliceosome (Map 18)
Method: EM (single particle) / Resolution: 2.82 Å

EMDB-50466: Structure of the C. elegans Intron Lariat Spliceosome (Map 19)
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-50467: Structure of the C. elegans Intron Lariat Spliceosome (Map 20)
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-50468: Structure of the C. elegans Intron Lariat Spliceosome (Map 21)
Method: EM (single particle) / Resolution: 6.33 Å

EMDB-50469: Structure of the C. elegans Intron Lariat Spliceosome (Map 22)
Method: EM (single particle) / Resolution: 3.13 Å

EMDB-50471: Structure of the C. elegans Intron Lariat Spliceosome (Map 23)
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-50472: Structure of the C. elegans Intron Lariat Spliceosome (Map 24)
Method: EM (single particle) / Resolution: 69968.0 Å

EMDB-50473: Structure of the C. elegans Intron Lariat Spliceosome (Map 25)
Method: EM (single particle) / Resolution: 3.94 Å

EMDB-50474: Structure of the C. elegans Intron Lariat Spliceosome (Map 27)
Method: EM (single particle) / Resolution: 4.19 Å

EMDB-50475: Structure of the C. elegans Intron Lariat Spliceosome (Map 26)
Method: EM (single particle) / Resolution: 3.91 Å

PDB-9fmd:
Integrative model of the human post-catalytic spliceosome (P-complex)
Method: ELECTRON MICROSCOPY / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

Source
  • caenorhabditis elegans (invertebrata)
  • homo sapiens (human)
  • human adenovirus 2
KeywordsSPLICING / mRNA / Intorn Lariat spliceosome / ILS / pre-mRNA / pre-mRNA splicing / intron lariat spliceosome / gene expression / spliceosome / P-complex

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