The Spliceosome is a Dynamic RNP Machine: Fidelity Strategies

Our long‐term goal is to understand at a molecular level the mechanisms responsible for specificity and fidelity in mRNA splicing. The splicing machinery is comprised of both RNA and protein components, which are organized as snRNPs. A unifying hypothesis that has emerged from our studies is that the assembly and catalytic function of the spliceosome involves extensive remodeling via the exchange of RNA:RNA and/or RNA:protein pairing partners that are, in some cases, mutually exclusive. This strategy enforces a highly ordered process and allows the opportunity for sequential inspections, or proofreading, to enforce the over‐all fidelity of splicing. Moreover, ATP‐dependent processes also couple the major steps of gene expression with one another. I will describe several significant recent advances in understanding the mechanism and biological significance of this dynamic design principle.