I will describe my lab's progress toward understanding the rules for exon recognition by the RNA splicing machinery in mammals. Current efforts are focused on systematic identification and characterization of sequences that function as exonic and intronic splicing silencers (ESS, ISS) and enhancers (ESE, ISE), using a combination of cell-based and computational screens. The identified splicing regulatory elements are being integrated with statistical models of the core splice site motifs into computer algorithms that simulate RNA splicing specificity. Recently, we have shown that ESS sequences play general roles in splice site definition at both the 5' and 3' splice sites, and we are investigating the mechanisms of this activity. We have also obtained evidence that ESS sequences are likely to control alternative 5' and 3' splice site usage in many exons, a common type of alternative splicing in mammals.
Host: Christine Wang