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RIG-I-driven CDKN1A stabilization reinforces cellular senescence

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收录情况： ◇ 统计源期刊 ◇ 卓越：领军期刊

作者：
Wang Cui[1,2,5] * ; Jiang Xiaoyu[3,5] * ; Li Hong-Yu[4,5] * ; Hu Jianli[1,2,5] ; Ji Qianzhao[3,5] ; Wang Qiaoran[1,2,5] ; Liu Xiaoqian[3,6] ; Huang Daoyuan[7,8] ; Yan Kaowen[3,6] ; Zhao Liyun[7,8] ; Fan Yanling[1,2] ; Wang Si[7,8,9] ; Ma Shuai[3,9] ; Belmonte Juan Carlos Izpisua[10] ; Qu Jing[3,5,7,9] ; Liu Guang-Hui[3,5,6,7,8,9] ; Zhang Weiqi[1,2,5,9] ;
机构： [1]China National Center for Bioinformation, Beijing 100101, China [2]Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [3]State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [4]Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [5]University of Chinese Academy of Sciences, Beijing 100049, China [6]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China [7]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China [8]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital Capital Medical University, Beijing 100053, China [9]Aging Biomarker Consortium, Beijing 100101, China [10]Altos Labs, Inc., San Diego, CA 94022, USA
出处：
DOI： 10.1007/s11427-024-2844-8
ISSN：

摘要：
The innate immune signaling network follows a canonical format for signal transmission. The innate immune pathway is crucial for defense against pathogens, yet its mechanistic crosstalk with aging processes remains largely unexplored. Retinoic acid-inducible gene-I (RIG-I), a key mediator of antiviral immunity within this pathway, has an enigmatic role in stem cell senescence. Our study reveals that RIG-I levels increase in human genetic and physiological cellular aging models, and its accumulation drives cellular senescence. Conversely, CRISPR/Cas9-mediated RIG-I deletion or pharmacological inhibition in human mesenchymal stem cells (hMSCs) confers resistance to senescence. Mechanistically, RIG-I binds to endogenous mRNAs, with CDKN1A mRNA being a prominent target. Specifically, RIG-I stabilizes CDKN1A mRNA, resulting in elevated CDKN1A transcript levels and increased p21Cip1 protein expression, which precipitates senescence. Collectively, our findings establish RIG-I as a post-transcriptional regulator of senescence and suggest potential targets for the mitigation of aging-related diseases.© 2025. Science China Press.

基金：
This work was supported by the National Natural Science Foundation of China (82192863, 82361148131, 82125011, 81921006, 92149301, 92168201, 82122024, 82322025, 82330044, 32341001, 92049304, 92049116, 32121001, 82071588, 82361148130, 8231101626, 82201714, 82271600), the National Key Research and Development Program of China (2020YFA0804000, 2022YFA1103700, 2020YFA0112200, the STI2030-Major Projects-2021ZD0202400, 2021YFF1201000, 2021YFA1101000), CAS Project for Young Scientists in Basic Research (YSBR-076, YSBR-012), the Program of the Beijing Natural Science Foundation (Z230011, Z240018, JQ24044), the Informatization Plan of Chinese Academy of Sciences (CASWX2022SDC- XK14), New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045), Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (JYY2023-13), CAS Youth Interdisciplinary Team, Key Laboratory of Alzheimer’s Disease of Zhejiang Province (ZJAD-2024001), Excellent Young Talents Program of Capital Medical University (12300927), The Project for Technology Development of Beijingaffiliated Medical Research Institutes (11000023T000002036310), Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105). Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Youth Innovation Promotion Association of CAS (2022083), The Fellowship of China Postdoctoral Science Foundation (2022M712216), and Initiative Scientific Research Program, Institute of Zoology, Chinese Academy of Sciences (2023IOZ0102).
语种：
外文
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中科院(CAS)分区：
出版当年[2025]版：
大类 | 1 区 生物学
小类 | 1 区 生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 生物学
第一作者：
第一作者机构： [1]China National Center for Bioinformation, Beijing 100101, China [2]Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [5]University of Chinese Academy of Sciences, Beijing 100049, China
共同第一作者：
通讯作者：
通讯机构： [1]China National Center for Bioinformation, Beijing 100101, China [2]Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [3]State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [5]University of Chinese Academy of Sciences, Beijing 100049, China [6]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China [7]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China [8]Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital Capital Medical University, Beijing 100053, China [9]Aging Biomarker Consortium, Beijing 100101, China
推荐引用方式(GB/T 7714)：
Wang Cui,Jiang Xiaoyu,Li Hong-Yu,et al.RIG-I-driven CDKN1A stabilization reinforces cellular senescence[J].Science China Life Sciences.2025,doi:10.1007/s11427-024-2844-8.
APA：
Wang Cui,Jiang Xiaoyu,Li Hong-Yu,Hu Jianli,Ji Qianzhao...&Zhang Weiqi.(2025).RIG-I-driven CDKN1A stabilization reinforces cellular senescence.Science China Life Sciences,,
MLA：
Wang Cui,et al."RIG-I-driven CDKN1A stabilization reinforces cellular senescence".Science China Life Sciences .(2025)

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