A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators

Pre-mRNA splicing is a crucial process in eukaryotic gene expression, and splicing dysregulation has been linked to various diseases. However, very few small molecules have been discovered to modulate spliced mRNA formation or inhibit the splicing machinery. This study presents a novel high-throughput screening (HTS) platform for identifying compounds that modulate splicing. Using this approach, we identified a compound that selectively kills human cancer cells containing a splicing factor mutation (SRSF2P95H) in tissue culture and causes widespread changes in gene expression in these cells relative to wildtype.