מושגי ליבה
The disassembly of the multi-megadalton spliceosome complex is initiated by the coordinated action of disassembly factors and the RNA helicase DHX15, which target the catalytic U6 snRNA to trigger the disassembly process after pre-mRNA splicing is complete.
תקציר
The article presents cryo-electron microscopy (cryo-EM) structures of the terminal intron-lariat spliceosome from nematodes and humans, along with biochemical and genetic data, to elucidate the mechanism of spliceosome disassembly.
Key insights:
Spliceosome disassembly is initiated by four disassembly factors and the conserved RNA helicase DHX15.
The disassembly factors probe the large inner and outer surfaces of the spliceosome to detect the release of the ligated mRNA.
Two disassembly factors, TFIP11 and C19L1, along with three general spliceosome subunits (SYF1, SYF2, and SDE2), dock and activate the DHX15 helicase on the catalytic U6 small nuclear RNA (snRNA) to trigger the disassembly process.
The U6 snRNA controls both the start and end of pre-mRNA splicing, as it is involved in the initiation of spliceosome assembly and the initiation of spliceosome disassembly.
The findings provide a framework to understand the general control of spliceosomal RNA helicases and the discard of aberrant spliceosomes.
סטטיסטיקה
The cryo-EM structures were determined at resolutions ranging from 2.6 to 3.2 Angstroms.
ציטוטים
"Our results uncover how four disassembly factors and the conserved RNA helicase DHX15 initiate spliceosome disassembly."
"U6 thus controls both the start and end of pre-mRNA splicing."