Intron lariat spliceosomes convert lariats to true circles: implications for intron transposition

Abstract

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 Saccharomyces cerevisiae, 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 during eukaryotic genome evolution.