Pre-mRNA splicing is a complex and error-prone process, and cells must identify and resolve spliceosomes that fail to complete catalysis. Although nuclear RNA surveillance has long been linked to the removal of aberrant transcripts, how it interfaces with splicing quality control has remained poorly understood.
In this talk, I will discuss our work on the mechanisms that recognise and resolve arrested spliceosomes. We have determined the structure of a quality-control intermediate and are using this framework to investigate how defects in spliceosome function are detected, how catalytic activity is restrained, and how stalled complexes are directed towards disassembly and RNA surveillance. Together, our results provide new insight into how the cell maintains the fidelity of gene expression when splicing goes wrong.