Dscam Alternative Splicing

Alternative splicing of pre-mRNA in higher eukaryotes is a key mechanism for expanding protein and transcript diversity. One of the most extreme examples is the Dscam gene in Drosophila melanogaster, which can generate up to 38,016 distinct isoforms through alternative splicing and is widely cited as a textbook paradigm. Over the past decade, our laboratory has focused on the molecular evolution, regulatory mechanisms, and biological functions of Dscam alternative splicing. We have established the central role of competing RNA secondary structures in mutually exclusive splicing, identified multiple modes of action for these structures, and developed a mechanistic framework for Dscam mutually exclusive splicing. In addition, we have systematically investigated the biological functions of Dscam1 isoform diversity and elucidated the underlying mechanisms.