Structural studies of the spliceosome: blind men and an elephant

Abstract

Proteomic studies have shown that spliceosomal complexes are massive, dynamic ribonucleoprotein assemblies that undergo extensive remodelling and exchange of components as spliceosomes are constructed, activated and recycled. Cryo-electron microscopy has revealed the overall shape of several spliceosomal complexes and the locations of key splicing factors. Over the last two years X-ray crystallography has produced the first detailed structure of a spliceosomal snRNP-the U1 snRNP from human-giving us important new insights into snRNP assembly and 5' splice site recognition. High-resolution structures of domains from the essential Brr2 and Prp8 splicing factors have shed new light on the mechanism of spliceosome activation and the interactions between Prp8 and the spliceosome's RNA core.