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TitleStructures of aberrant spliceosome intermediates on their way to disassembly.
Journal, issue, pagesNat Struct Mol Biol, Vol. 32, Issue 5, Page 914-925, Year 2025
Publish dateJan 20, 2025
AuthorsKomal Soni / Attila Horvath / Olexandr Dybkov / Merlin Schwan / Sasanan Trakansuebkul / Dirk Flemming / Klemens Wild / Henning Urlaub / Tamás Fischer / Irmgard Sinning /
PubMed AbstractIntron removal during pre-mRNA splicing is of extraordinary complexity and its disruption causes a vast number of genetic diseases in humans. While key steps of the canonical spliceosome cycle have ...Intron removal during pre-mRNA splicing is of extraordinary complexity and its disruption causes a vast number of genetic diseases in humans. While key steps of the canonical spliceosome cycle have been revealed by combined structure-function analyses, structural information on an aberrant spliceosome committed to premature disassembly is not available. Here, we report two cryo-electron microscopy structures of post-B spliceosome intermediates from Schizosaccharomyces pombe primed for disassembly. We identify the DEAH-box helicase-G-patch protein pair (Gih35-Gpl1, homologous to human DHX35-GPATCH1) and show how it maintains catalytic dormancy. In both structures, Gpl1 recognizes a remodeled active site introduced by an overstabilization of the U5 loop I interaction with the 5' exon leading to a single-nucleotide insertion at the 5' splice site. Remodeling is communicated to the spliceosome surface and the Ntr1 complex that mediates disassembly is recruited. Our data pave the way for a targeted analysis of splicing quality control.
External linksNat Struct Mol Biol / PubMed:39833470 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.2 Å
Structure data

19941

9esh

EMDB-19941, PDB-9esh:
Structure of a B-state intermediate committed to discard (Bd-I state)
Method: EM (single particle) / Resolution: 3.2 Å

19942

9esi

EMDB-19942, PDB-9esi:
Structure of a B-state intermediate committed to discard (Bd-II state)
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

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

ChemComp-ZN:
Unknown entry

Source
  • schizosaccharomyces pombe (fission yeast)
KeywordsSPLICING / Helicase / G-patch protein / discard pathway

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