Unravelling the molecular basis of fidelity in mRNA splicing

Splicing of pre-mRNA is a crucial process in gene expression in eukaryotes, linked to human diseases such as cancer. It is catalysed by the spliceosome, a large protein-RNA complex which undergoes major conformational and compositional changes to enable the splicing reactions and release of the spliced mRNA. Structural characterisation by CryoEM and X-ray crystallography have greatly enhanced the understanding of the molecular basis of splicing. However, the processes ensuring proofreading and fidelity mechanisms of the splicing remain structurally poorly understood. This project aims to elucidate these processes by the structural characterization of fidelity complexes identified in our laboratories by cryoEM.