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Global intron retention mediated gene regulation during CD4+ T cell activation

Ting Ni,Wenjing Yang,M. Han,Yubo Zhang,T. Shen,H. Nie,Zhihui Zhou,Yalei Dai,Yanqin Yang,Poching Liu,Kairong Cui,Zhouhao Zeng,Yiwen Tian,Bin Zhou,Gang Wei,K. Zhao,Weiqun Peng,Jun Zhu

Published 2016 in Nucleic Acids Research

ABSTRACT

T cell activation is a well-established model for studying cellular responses to exogenous stimulation. Using strand-specific RNA-seq, we observed that intron retention is prevalent in polyadenylated transcripts in resting CD4+ T cells and is significantly reduced upon T cell activation. Several lines of evidence suggest that intron-retained transcripts are less stable than fully spliced transcripts. Strikingly, the decrease in intron retention (IR) levels correlate with the increase in steady-state mRNA levels. Further, the majority of the genes upregulated in activated T cells are accompanied by a significant reduction in IR. Of these 1583 genes, 185 genes are predominantly regulated at the IR level, and highly enriched in the proteasome pathway, which is essential for proper T cell proliferation and cytokine release. These observations were corroborated in both human and mouse CD4+ T cells. Our study revealed a novel post-transcriptional regulatory mechanism that may potentially contribute to coordinated and/or quick cellular responses to extracellular stimuli such as an acute infection.

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