IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34434-y.html
   My bibliography  Save this article

METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury

Author

Listed:
  • Lijun Wang

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • Jiaqi Wang

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • Pujiao Yu

    (Tongji University School of Medicine)

  • Jingyi Feng

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • Gui-e Xu

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • Xuan Zhao

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • Tianhui Wang

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

  • H. Immo Lehmann

    (Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School)

  • Guoping Li

    (Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School)

  • Joost P. G. Sluijter

    (University Medical Center Utrecht
    University Medical Center Utrecht, University Utrecht)

  • Junjie Xiao

    (Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People’s Hospital of Nantong), School of Medicine, Shanghai University
    Shanghai University)

Abstract

RNA m6A modification is the most widely distributed RNA methylation and is closely related to various pathophysiological processes. Although the benefit of regular exercise on the heart has been well recognized, the role of RNA m6A in exercise training and exercise-induced physiological cardiac hypertrophy remains largely unknown. Here, we show that endurance exercise training leads to reduced cardiac mRNA m6A levels. METTL14 is downregulated by exercise, both at the level of RNA m6A and at the protein level. In vivo, wild-type METTL14 overexpression, but not MTase inactive mutant METTL14, blocks exercise-induced physiological cardiac hypertrophy. Cardiac-specific METTL14 knockdown attenuates acute ischemia-reperfusion injury as well as cardiac dysfunction in ischemia-reperfusion remodeling. Mechanistically, silencing METTL14 suppresses Phlpp2 mRNA m6A modifications and activates Akt-S473, in turn regulating cardiomyocyte growth and apoptosis. Our data indicates that METTL14 plays an important role in maintaining cardiac homeostasis. METTL14 downregulation represents a promising therapeutic strategy to attenuate cardiac remodeling.

Suggested Citation

  • Lijun Wang & Jiaqi Wang & Pujiao Yu & Jingyi Feng & Gui-e Xu & Xuan Zhao & Tianhui Wang & H. Immo Lehmann & Guoping Li & Joost P. G. Sluijter & Junjie Xiao, 2022. "METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34434-y
    DOI: 10.1038/s41467-022-34434-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34434-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-34434-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ralf Gilsbach & Martin Schwaderer & Sebastian Preissl & Björn A. Grüning & David Kranzhöfer & Pedro Schneider & Thomas G. Nührenberg & Sonia Mulero-Navarro & Dieter Weichenhan & Christian Braun & Mart, 2018. "Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Xiang Wang & Jing Feng & Yuan Xue & Zeyuan Guan & Delin Zhang & Zhu Liu & Zhou Gong & Qiang Wang & Jinbo Huang & Chun Tang & Tingting Zou & Ping Yin, 2016. "Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex," Nature, Nature, vol. 534(7608), pages 575-578, June.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tianbao Ye & Cheng Chen & Di Wang & Chengjie Huang & Zhiwen Yan & Yu Chen & Xian Jin & Xiuyuan Wang & Xianting Ding & Chengxing Shen, 2024. "Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Na Chen & Lizhe Guo & Lu Wang & Sisi Dai & Xiaocheng Zhu & E. Wang, 2024. "Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhiyuan Luo & Jiacheng Zhang & Jingyi Fei & Shengdong Ke, 2022. "Deep learning modeling m6A deposition reveals the importance of downstream cis-element sequences," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Qiang Luo & Jiezhen Mo & Hao Chen & Zetao Hu & Baihui Wang & Jiabing Wu & Ziyu Liang & Wenhao Xie & Kangxi Du & Maolin Peng & Yingping Li & Tianyang Li & Yangyi Zhang & Xiaoyan Shi & Wen-Hui Shen & Ya, 2022. "Structural insights into molecular mechanism for N6-adenosine methylation by MT-A70 family methyltransferase METTL4," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Belinda Baquero-Pérez & Ivaylo D. Yonchev & Anna Delgado-Tejedor & Rebeca Medina & Mireia Puig-Torrents & Ian Sudbery & Oguzhan Begik & Stuart A. Wilson & Eva Maria Novoa & Juana Díez, 2024. "N6-methyladenosine modification is not a general trait of viral RNA genomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Jiyun Chen & Rong Hu & Ying Chen & Xiaofeng Lin & Wenwen Xiang & Hong Chen & Canglin Yao & Liang Liu, 2022. "Structural basis for MTA1c-mediated DNA N6-adenine methylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Huaxia Shi & Ying Xu & Na Tian & Ming Yang & Fu-Sen Liang, 2022. "Inducible and reversible RNA N6-methyladenosine editing," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Tianye Zhang & Chaonan Shi & Haichao Hu & Zhuo Zhang & Ziqiong Wang & Zhiqing Chen & Huimin Feng & Peng Liu & Jun Guo & Qisen Lu & Kaili Zhong & ZhiHui Chen & Jiaqian Liu & Jiancheng Yu & Jianping Che, 2022. "N6-methyladenosine RNA modification promotes viral genomic RNA stability and infection," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Yan Xu & Zhuowei Zhou & Xinmei Kang & Lijie Pan & Chang Liu & Xiaoqi Liang & Jiajie Chu & Shuai Dong & Yanli Li & Qiuli Liu & Yuetong Sun & Shanshan Yu & Qi Zhang, 2022. "Mettl3-mediated mRNA m6A modification controls postnatal liver development by modulating the transcription factor Hnf4a," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Katja Hartstock & Nadine A. Kueck & Petr Spacek & Anna Ovcharenko & Sabine Hüwel & Nicolas V. Cornelissen & Amarnath Bollu & Christoph Dieterich & Andrea Rentmeister, 2023. "MePMe-seq: antibody-free simultaneous m6A and m5C mapping in mRNA by metabolic propargyl labeling and sequencing," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Xiang Zhang & Huilong Yin & Xiaofang Zhang & Xunliang Jiang & Yongkang Liu & Haolin Zhang & Yingran Peng & Da Li & Yanping Yu & Jinbao Zhang & Shuli Cheng & Angang Yang & Rui Zhang, 2022. "N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Yaodong Zhang & Zijian Ma & Changxian Li & Cheng Wang & Wangjie Jiang & Jiang Chang & Sheng Han & Zefa Lu & Zicheng Shao & Yirui Wang & Hongwei Wang & Chenyu Jiao & Dong Wang & Xiaofeng Wu & Hongbing , 2022. "The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34434-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.