biostudies-literatureAres MNational Institute of General Medical SciencesNIGMS NIH HHS322-335https://www.ebi.ac.uk/biostudies/studies/S-EPMC11146597biostudies-literatureUnknown38(7-8)Rare, full-length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envisioned and tested a hypothesis for their formation using <i>Saccharomyces cerevisiae</i>, documenting full-length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron lariat spliceosome (ILS) in which the 3'-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3' processing machinery) attacks the branch, joining the intron 3' end to the 5' splice site in a 3'-5' linked circle. Human U2 and U12 spliceosomes produce analogous full-length and processed circles. Postsplicing catalytic activity of the spliceosome may promote intron transposition Genes & developmentIntron lariat spliceosomes convert lariats to true circles: implications for intron transposition.PMC11146597R01 GM040478R35 GM145266Donohue JPIgel HAres MKatzman SfalseIntron lariat spliceosomes convert lariats to true circles: implications for intron transposition.Rare, full-length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envisioned and tested a hypothesis for their formation using <i>Saccharomyces cerevisiae</i>, documenting full-length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron lariat spliceosome (ILS) in which the 3'-OH of the lariat tail (with optional trimming and adenylation by the nuclear 3' processing machinery) attacks the branch, joining the intron 3' end to the 5' splice site in a 3'-5' linked circle. Human U2 and U12 spliceosomes produce analogous full-length and processed circles. Postsplicing catalytic activity of the spliceosome may promote intron transposition 2024-01-01T00:00:00Z2024 May2026-06-02T23:22:56.589Z2025-04-04T07:40:50.314ZS-EPMC111465973872420910.1101/gad.351764.124