Manuel Ares Jr.1,2, Haller Igel1, Sol Katzman1,2 and John P. Donohue1 1Center for Molecular Biology of RNA, University of California, Santa Cruz, Santa Cruz, California 95064, USA; 2Genomics Institute, University of California, Santa Cruz, Santa Cruz, California 95064, USA Corresponding author: aresucsc.edu 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.

Received March 30, 2024. Accepted April 24, 2024.