The mechanism of splicing as told by group II introns: Ancestors of the spliceosome

Abstract

Spliceosomal introns and self-splicing group II introns share a common mechanism of intron splicing where two sequential transesterification reactions remove intron lariats and ligate exons. The recent revolution in cryo-electron microscopy (cryo-EM) has allowed visualization of the spliceosome's ribozyme core. Comparison of these cryo-EM structures to recent group II intron crystal structures presents an opportunity to draw parallels between the RNA active site, substrate positioning, and product formation in these two model systems of intron splicing. In addition to shared RNA architectural features, structural similarity between group II intron encoded proteins (IEPs) and the integral spliceosomal protein Prp8 further support a shared catalytic core. These mechanistic and structural similarities support the long-held assertion that group II introns and the eukaryotic spliceosome have a common evolutionary origin. In this review, we discuss how recent structural insights into group II introns and the spliceosome facilitate the chemistry of splicing, highlight similarities between the two systems, and discuss their likely evolutionary connections. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.