CIS-regulatory Circuitry of Polypyrimidine Binding Proteins

Brown University, Providence RI

Investigators

Abstract

Intellectual Merit: Understanding how proteins work together to regulate gene expression is a fundamental problem in cellular biochemistry. This research focuses on a regulator of gene expression called the polypyrimidine tract binding protein (PTB), which binds to specific pyrimidine-rich regions in pre-messenger RNA molecules to regulate pre-mRNA splicing. How PTB recognizes its specific binding sites in RNA remains an unanswered question, which this research seeks to address by testing the hypothesis that specificity is conferred, in part, by association of PTB with other RNA binding proteins. Building on a recent map of cellular PTB binding sites, this research will define how PTB interacts with other RNA binding proteins. A novel high throughput binding assay will be used to map PTB and its interacting partners onto RNA. The overlay of the maps will suggest synergistic relationships that will be tested in vivo. Broader Impacts: This research will provide training for graduate and undergraduate students at the cross-disciplinary interface between molecular biology and computational science. The data generated by the project will be used for computational analysis by summer undergraduate students participating in an internship program in biological mathematics. The project will also offer opportunities for postdoctoral training and for members of underrepresented groups to participate in research.