Principal Investigator Phillip Sharp
Changes in alternative splicing of genes is essential for normal development and many disease processes. We have recently completed a study mapping the binding of Rbfox2 to precursor RNA in mouse embryonic stem cells and found that this factor controls alternative splicing of many other RNA binding proteins shifting their threshold of auto-regulation and thus broadly controlling splicing of thousands of genes. In a parallel study, we found that a subset of introns is spliced more slowly in cells than their downstream neighbors and some of the precursor RNA is detained in the nucleus and degraded. A fraction of these detained introns becomes rapidly processed if phosphorylation of SR proteins is inhibited. This uncovers a new point of splicing regulation probably responding to stress and activation of signaling pathways.