9is7

Publication Abstract from PubMed

Circularly permuted group II introns (CP introns) consist of rearranged structural domains separated by two tethered exons, generating branched introns and circular exons via back-splicing. Structural and mechanistic understanding of circular RNA (circRNA) generation by CP introns remains elusive. We resolve cryo-electron microscopy structures of a natural CP intron in different states during back-splicing at a resolution of 2.5-2.9 A. Domain 6 (D6) undergoes a conformational change of 65 degrees after branching, to facilitate 3'-exon recognition and circularization. Previously unseen tertiary interactions compact the catalytic triad and D6 for splicing without protein, whereas a metal ion, M(35), is observed to stabilize the 5'-exon during splicing. While these unique features were not observed in canonical group II introns and spliceosomes, they are common in CP introns, as demonstrated by the cryo-EM structure of another CP intron discovered by comparative genomics analysis. Our results elucidate the mechanism of CP intron back-splicing dynamics, with potential applications in circRNA research and therapeutics.

Structural basis of circularly permuted group II intron self-splicing.,Wang L, Xie J, Zhang C, Zou J, Huang Z, Shang S, Chen X, Yang Y, Liu J, Dong H, Huang D, Su Z Nat Struct Mol Biol. 2025 Jan 31. doi: 10.1038/s41594-025-01484-x. PMID:39890981^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.