Abstract:
:The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.
journal_name
Naturejournal_title
Natureauthors
Li X,Liu S,Zhang L,Issaian A,Hill RC,Espinosa S,Shi S,Cui Y,Kappel K,Das R,Hansen KC,Zhou ZH,Zhao Rdoi
10.1038/s41586-019-1523-6subject
Has Abstractpub_date
2019-09-01 00:00:00pages
375-380issue
7774eissn
0028-0836issn
1476-4687pii
10.1038/s41586-019-1523-6journal_volume
573pub_type
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