Nuclear pre-mRNA Splicing
Nuclear pre-mRNA splicing is ubiquitious in all eukaryotes and is required to excise introns before mRNA is translated by the ribosome. Further, splicing enables a critical layer in the regulation of gene expression as well as a flexibility through alternative splicing that affords complexity in higher organisms, but splicing is also susceptible to mutations and underlies at least 15% of human diseases.
Splicing is mediated by the spliceosome, a dynamic machine composed of both protein and noncoding RNA (ncRNA) parts. Our lab investigates the role of these ncRNA components in substrate binding and catalysis, the mechanisms for proofreading splice site choice, the role for ATPases in dynamics and fidelity, and the regulation of splicing. Primarily using budding yeast as a model system, we pursue these areas through a wide range of approaches, from single molecule microscopy and chemical biology to biochemistry, genetics, and genomics.