Structure and assembly of the spliceosomal snRNPs. Novartis Medal Lecture.

The spliceosome is a macromolecular machine that carries out the excision of introns from eukaryotic pre-mRNAs and splicing together of exons. Four large RNA-protein complexes, called the U1, U2, U4/U6 and U5 small nuclear ribonucleoprotein particles (snRNPs), and some non-snRNP proteins assemble around three short conserved sequences within the intron in an ordered manner to form the active spliceosome. We aim to provide insight into the molecular details of the mechanism of pre-mRNA splicing through crystallographic studies of the snRNPs. We have solved the X-ray crystal structure of some snRNP proteins as part of either protein-protein complexes or RNA-protein complexes. These structures have provided an important insight into the overall architecture of the U1 and U2 snRNPs and the mechanisms of RNA-protein and protein-protein recognition.