Format

Send to

Choose Destination
Nucleic Acids Res. 2016 Aug 19;44(14):6817-29. doi: 10.1093/nar/gkw591. Epub 2016 Jul 1.

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

Author information

1
State Key Laboratory of Genetic Engineering & MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, P.R. China tingni@fudan.edu.cn.
2
Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
3
State Key Laboratory of Genetic Engineering & MOE Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, P.R. China.
4
Department of Immunology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
5
Department of Physics, George Washington University, Washington, DC 20052, USA.
6
Department of Physics, George Washington University, Washington, DC 20052, USA Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, P.R. China.
7
Department of Physics, George Washington University, Washington, DC 20052, USA wpeng@gwu.edu.
8
Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA jun.zhu@nih.gov.

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.

PMID:
27369383
PMCID:
PMC5001615
DOI:
10.1093/nar/gkw591
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center