MiRNA post-transcriptional modification dynamics in T cell activation

Abstract

T cell activation leads to extensive changes in the miRNA repertoire. Although overall miRNA expression decreases within a few hours of T cell activation, some individual miRNAs are specifically upregulated. Using next-generation sequencing, we assessed miRNA expression and post-transcriptional modification kinetics in human primary CD4+ T cells upon T cell receptor (TCR) or type I interferon stimulation. This analysis identified differential expression of multiple miRNAs not previously linked to T cell activation. Remarkably, upregulated miRNAs showed a higher frequency of 3′ adenylation. TCR stimulation was followed by increased expression of RNA modifying enzymes and the RNA degrading enzymes Dis3L2 and Eri1. In the midst of this adverse environment, 3′ adenylation may serve a protective function that could be exploited to improve miRNA stability for T cell-targeted therapy.