Reference - PMID:39833470 - Structures of aberrant spliceosome intermediates on their way to disassembly.
Reference summary
- PubMed ID
- PMID:39833470
- Title
- Structures of aberrant spliceosome intermediates on their way to disassembly.
- Authors
- Soni K, Horvath A, Dybkov O, Schwan M, Trakansuebkul S, Flemming D, Wild K, Urlaub H, Fischer T, Sinning I
- Citation
- Nat Struct Mol Biol 2025 Jan 20;
- Publication year
- 2025
- 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-B act 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.
