Conserved Proline-Directed Phosphorylation Regulates SR Protein Conformation and Splicing Function

In this study, we address the effects of discrete serine-proline phosphorylation on the conformation and cellular function of the SR protein SRSF1. Using chemical tagging and dephosphorylation experiments, we show that modification of serine-proline dipeptides broadly amplifies the conformational ensemble of SRSF1. The induction of these new structural forms triggers SRSF1 mobilization in the nucleus and alters its binding mechanism to an exonic splicing enhancer in precursor mRNA. These physical events correlate with changes in the alternative splicing of over one hundred human genes based on a global splicing assay. Overall, these studies draw a direct causal relationship between a specific type of chemical modification in an SR protein and the regulation of alternative gene splicing programs.

Source: BJ Signal - December 22, 2014 Category: Biochemistry Authors: M M Keshwani, B E. Aubol, L Fattet, C Ma, J Qiu, P A. Jennings, X Fu, J A. Adams Tags: BJ Signal Source Type: research