Welcome to the Spliceosome Group page

The spliceosome is a molecular machine that catalyses the removal of introns from mRNA precursors (pre-mRNAs).  It consists of five RNA-protein complexes (snRNPs) which assemble onto pre-mRNA substrates in an ordered manner.  One of these, U1 snRNP, binds to the 5’ splice site (the junction between exon and intron) in mRNA precursors.  It consists of U1 snRNA and ten proteins.  Recently we reported the structure of U1 snRNP (Nature 458, 457-480 (2009)).  Its striking feature is the extended N-terminal polypeptide of U1-70k which wraps around the core domain and stabilises the binding of U1-C (red)).  The structure also reveals how U1 snRNP binds the 5’ splice site of pre-mRNAs.  We have just published the structure of the U4 snRNP core domain at 3.6Å resolution (Nature (2011) doi:10.1038/Nature09956).  The structure has revealed how the Sm site heptad (AUUUUUG) binds inside the central hole of the  heptameric ring of Sm  proteins, interacting one-to-one with SmE-SmG-SmD3-SmB-SmD1-SmD2-SmF proteins.  The snRNP core domain is present in U1, U2, U4 and U5 snRNPs.  A comparison between the U4 core and the U1 snRNP structures has revealed snRNA-dependent structural changes of the core domain outside the Sm fold, which allow specific binding of particle specific proteins that are crucial to biogensis of spliceosomal snRNPs.