Molecular Recognition During pre-mRNA Splicing (NIH R01 GM070503)

The overall goal of this research is to understand how essential ternary complexes of SF1, U2AF65, and U2AF35 splicing factors recognizes 3´ splice sites and initiates the process of spliceosome assembly. Specifically, we will: (i) Determine the three-dimensional shape of the full assembly of human splicing proteins bound to the gene transcript; (ii) Understand the function of splicing factor phosphorylation and its potential to serve as a drug target; (iii) Leverage emerging views of splice site signal recognition as a basis to predictably target and correct defective splice sites. The proposed research will show the molecular underpinnings of 3´ splice site selection, and thus have ramifications for understanding and potentially correcting pre-mRNA splicing defects in human diseases.

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