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

Genes Dev. 2024 May 21;38(7-8):322-335. doi: 10.1101/gad.351764.124.

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.

Keywords: circular RNA; intron transposition; reverse splicing.

MeSH terms

  • Humans
  • Introns* / genetics
  • RNA / genetics
  • RNA / metabolism
  • RNA Splicing* / genetics
  • RNA, Circular / genetics
  • RNA, Circular / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Spliceosomes* / genetics
  • Spliceosomes* / metabolism