12.00pm Monday, 26 February
2nd floor, Microbiology Building
720 Cumberland St
MRC Laboratory for Molecular Biology
Introns are removed from pre-messenger RNA by a large, dynamic molecular machine called the spliceosome. The spliceosome assembles on pre-mRNA by the ordered assembly of the small nuclear ribonucleoprotein particles (U1, U2, U4/U6 and U5 snRNPs) and catalyses two sequential reactions: branching, where a conserved adenosine in the intron attacks the 5’ splice site; and exon ligation, where the 5’-exon attacks the 3’ splice site, forming mature mRNA and the excised lariat-intron. The snRNAs form the core of the spliceosome and are directly responsible for catalysis and intron recognition. Despite decades of work, the spliceosome has defied structural characterisation due to its low abundance, large size, and extreme flexibility: problems that recent developments in electron cryomicroscopy (cryoEM) can circumvent. In this talk I will present near-atomic resolution cryoEM structures of the spliceosome carrying out the two chemical steps of splicing. These structures reveal the architecture of this immense molecular machine and the structural basis for splice site selection, showing how proteins cradle and modulate a fundamentally RNA-based mechanism of splicing catalysis.
This seminar is kindly sponsored by: BD Biosciences