Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3' end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3' untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3' end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation.
Bibliographical noteFunding Information:
We thank the Biomedical Genomics Center and the Minnesota Supercomputing Institute at the University of Minnesota for their expertise and services. This work was supported by NIH grants AI057484 , AI072068 and AI096925 to P.R.B. D.B. was supported by NIH grant 3T32GM8244-24S2 .
- Alternative polyadenylation
- Cell division
- MRNA decay
- T cell stimulation