title: Global intron retention mediated gene regulation during CD4+ T cell activation.
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.
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Ni
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Miao
authors.initials: M
authors.lastname: Han
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ting
authors.initials: T
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Immunology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Immunology, Tongji University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Yalei
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Poching
authors.initials: P
authors.lastname: Liu
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.affiliation: Department of Physics, George Washington University, Washington, DC 20052, USA.
authors.forename: Zhouhao
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Physics, George Washington University, Washington, DC 20052, USA Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Physics, George Washington University, Washington, DC 20052, USA wpeng@gwu.edu.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Peng
authors.affiliation: Systems Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA jun.zhu@nih.gov.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C488765:PSMD7 protein, human; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex