Department of Biochemistry and Biophysics - Perelman School of Medicine, University of Pennsylvania

__________

Host:  Walter Moss

__________

"Signal-Responsive RNA Processing in the Human Immune System: A Story of CELF Control"

The 3’ untranslated region (UTR) of human mRNAs contain sequences that play a critical role in controlling mRNA stability, localization and translation of the upstream open reading frame. Therefore the identity of the 3’ UTR has a profound impact on protein expression. Importantly, 3’UTRs of human messages are not invariant for each gene, but rather are subject to regulation by alternative splicing and alternative polyadenylation. In particular, alternative polyadenylation (APA) is a widespread phenomenon in human cells that controls protein expression by altering where the message is cleaved for polyadenylation, thus determining the presence or absence of the sequences between APA sites.  Broad regulation of APA has been observed during many transitions in cell state, including in response to T cell activation; however, the mechanisms driving this regulation remain poorly understood.

Previously, we have identified the RNA binding protein CELF2 as an activation-dependent regulator of alternative splicing during T cell development and in response to signaling in a cultured T cell line. Here we show that CELF2 also controls APA, as well as regulating introns within 3’UTRs. Together these activities shape 3’UTR identity in a condition specific manner. Therefore these studies uncover a new mechanism by which APA is regulated in a signal-dependent manner in T cells.