The Staley Lab’s goal is to understand the mechanisms that underlie nuclear pre-mRNA splicing, an essential step in eukaryotic gene expression. Pre-mRNA splicing is catalyzed by a massive multimegadalton ribonucleoprotein machine called the spliceosome. Using the model organism S. cerevisiae, we apply genetic, biochemical, single molecule, and genomic approaches to gain a deeper understanding of how the spliceosome catalyzes and regulates pre-mRNA splicing.