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Structure paper

TitleMechanism for the initiation of spliceosome disassembly.
Journal, issue, pagesNature, Year 2024
Publish dateJun 26, 2024
AuthorsMatthias K Vorländer / Patricia Rothe / Justus Kleifeld / Eric Cormack / Lalitha Veleti / Daria Riabov-Bassat / Laura Fin / Alex W Phillips / Luisa Cochella / Clemens Plaschka /
PubMed AbstractPre-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.
External linksNature / PubMed:38925148
MethodsEM (single particle)
Resolution2.73 - 69968.0 Å
Structure data


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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


EMDB entry, No image

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-K:
Unknown entry

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

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

ChemComp-ZN:
Unknown entry

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

Source
  • Caenorhabditis elegans (invertebrata)
  • homo sapiens (human)
  • human adenovirus 2
KeywordsSPLICING / P-complex / spliceosome

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