CryoEM structures of spliceosomal complexes reveal the molecular mechanism of pre-mRNA splicing.

The spliceosome is an intricate molecular machine which catalyses the removal of introns from eukaryotic mRNA precursors by two trans-esterification reactions (branching and exon ligation) to produce mature mRNA with uninterrupted protein coding sequences. The structures of the spliceosome in several key states determined by electron cryo-microscopy have greatly advanced our understanding of its molecular mechanism. The catalytic RNA core is formed during the activation of the fully assembled B to Bact complex and remains largely unchanged throughout the splicing cycle. RNA helicases and step specific factors regulate docking and undocking of the substrates (branch site and 3' splice site) to the single RNA-based active site to catalyse the two trans-esterification reactions.