Induced Transcription and Stability of CELF2 Mrna Drives Widespread Alternative Splicing During T-cell Signaling

SignificanceAlternative splicing is a key mechanism for gene regulation that is regulated in response to developmental and antigen signaling in T cells. However, the extent and mechanisms of regulated splicing, particularly during T-cell development, have not been well characterized. Here we demonstrate that expression of the RNA binding protein CELF2 (CUGBP, Elav-like family member 2) is increased in response to T-cell signaling through the combined regulation of transcription and mRNA stability. This increase in CELF2 expression drives widespread changes in mRNA splicing in cultured T cells and correlates with changes in mRNA splicing during T-cell development. These results provide unprecedented insight into the regulation of splicing during thymic development, and reveal an important biologic role of CELF2 in human T cells.