GSE183424
Dynamic 3'UTR changes during naïve CD4+ T cell activation and proliferation are reverted in the effector/memory state [A-Seq]
3' untranslated regions (3'UTRs) are critical elements of most messenger RNA species and can contain binding sites for RNA-binding proteins (RBP) and microRNAs that affect various aspects of RNA life cycles including transcript stability. Cells of the adaptive immune system undergo massive expansion during the effector phase of the immune response and dynamically modify their 3'UTRs in a response to T cell receptor activation. Whether this phenomenon is a secondary effect of proliferation or a mechanism to directly regulate the abundance of specific mRNAs remains unclear. To study 3'UTR dynamics in T helper cells we investigated division-dependent alternative polyadenylation and observed a transient character of global 3'UTR shortening/lengthening in T helper cells that return to a naïve-like polyadenylation state after effector phase expansion. We also showed that 3'UTR lengthening is associated with higher transcript abundance and post-transcriptional regulation than 3'UTR shortening. Sequence analysis of conserved microRNA and RBP binding sites located within varying 3' UTR regions highlighted the putative involvement of several microRNAs during this process. Our study emphasizes the value of polyadenylation isoforms analysis for understanding cell behaviors, revealing new aspects of the highly complex interplay of transcriptional and post-transcriptional layers in triggering transcript abundance. Overall design: Examination of 3'UTR polyadenylation site dynamics