Position-dependent activity of CELF2 in the regulation of splicing and implications for signal-responsive regulation in T cells

Sandya Ajith, Matthew R. Gazzara, Brian S. Cole, Ganesh Shankarling, Nicole M. Martinez, Michael J. Mallory, Kristen W. Lynch
2016 Figshare  
CELF2 is an RNA binding protein that has been implicated in developmental and signal-dependent splicing in the heart, brain and T cells. In the heart, CELF2 expression decreases during development, while in T cells CELF2 expression increases both during development and in response to antigen-induced signaling events. Although hundreds of CELF2-responsive splicing events have been identified in both heart and T cells, the way in which CELF2 functions has not been broadly investigated. Here we
more » ... tigated. Here we use CLIP-Seq to identified physical targets of CELF2 in a cultured human T cell line. By comparing the results with known functional targets of CELF2 splicing regulation from the same cell line we demonstrate a generalizable position-dependence of CELF2 activity that is consistent with previous mechanistic studies of individual CELF2 target genes in heart and brain. Strikingly, this general position-dependence is sufficient to explain the bi-directional activity of CELF2 on 2 T cell targets recently reported. Therefore, we propose that the location of CELF2 binding around an exon is a primary predictor of CELF2 function in a broad range of cellular contexts.
doi:10.6084/m9.figshare.3187585 fatcat:y52ry7gvhbgalk2fchx55urzsy