EMD-19942
Structure of a B-state intermediate committed to discard (Bd-II state)
EMD-19942
Single-particle3.1 Å
Deposition: 26/03/2024
Map released: 25/12/2024
Last modified: 29/01/2025
Sample Organism:
Schizosaccharomyces pombe
Sample: Bd-II complex
Fitted models: 9esi
Deposition Authors: Soni K , Wild K , Sinning I
Sample: Bd-II complex
Fitted models: 9esi
Deposition Authors: Soni K , Wild K , Sinning I
Structures of aberrant spliceosome intermediates on their way to disassembly.
Soni K ,
Horvath A,
Dybkov O,
Schwan M,
Trakansuebkul S,
Flemming D ,
Wild K ,
Urlaub H ,
Fischer T ,
Sinning I
(2025) Nat Struct Mol Biol
(2025) Nat Struct Mol Biol
Abstract:
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-Bact 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.
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-Bact 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.