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FTO-dependent m6A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke

Author

Listed:
  • Bin Li

    (Southeast University)

  • Wen Xi

    (Southeast University)

  • Ying Bai

    (Southeast University)

  • Xue Liu

    (Southeast University)

  • Yuan Zhang

    (Southeast University)

  • Lu Li

    (Southeast University)

  • Liang Bian

    (Southeast University)

  • Chenchen Liu

    (Southeast University)

  • Ying Tang

    (Southeast University)

  • Ling Shen

    (Southeast University)

  • Li Yang

    (Southeast University)

  • Xiaochun Gu

    (Medical School of Southeast University)

  • Jian Xie

    (Southeast University)

  • Zhongqiu Zhou

    (Southeast University)

  • Yu Wang

    (Southeast University)

  • Xiaoyu Yu

    (Southeast University)

  • Jianhong Wang

    (Chinese Academy of Sciences)

  • Jie Chao

    (Southeast University)

  • Bing Han

    (Southeast University)

  • Honghong Yao

    (Southeast University
    Nantong University
    Southeast University)

Abstract

Vascular repair is considered a key restorative measure to improve long-term outcomes after ischemic stroke. N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNAs, functionally mediates vascular repair. However, whether circular RNA SCMH1 (circSCMH1) promotes vascular repair by m6A methylation after stroke remains to be elucidated. Here, we identify the role of circSCMH1 in promoting vascular repair in peri-infarct cortex of male mice and male monkeys after photothrombotic (PT) stroke, and attenuating the ischemia-induced m6A methylation in peri-infarct cortex of male mice after PT stroke. Mechanically, circSCMH1 increased the translocation of ubiquitination-modified fat mass and obesity-associated protein (FTO) into nucleus of endothelial cells (ECs), leading to m6A demethylation of phospholipid phosphatase 3 (Plpp3) mRNA and subsequently the increase of Plpp3 expression in ECs. Our data demonstrate that circSCMH1 enhances vascular repair via FTO-regulated m6A methylation after stroke, providing insights into the mechanism of circSCMH1 in promoting stroke recovery.

Suggested Citation

  • Bin Li & Wen Xi & Ying Bai & Xue Liu & Yuan Zhang & Lu Li & Liang Bian & Chenchen Liu & Ying Tang & Ling Shen & Li Yang & Xiaochun Gu & Jian Xie & Zhongqiu Zhou & Yu Wang & Xiaoyu Yu & Jianhong Wang &, 2023. "FTO-dependent m6A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36008-y
    DOI: 10.1038/s41467-023-36008-y
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    References listed on IDEAS

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    2. Xiao Wang & Zhike Lu & Adrian Gomez & Gary C. Hon & Yanan Yue & Dali Han & Ye Fu & Marc Parisien & Qing Dai & Guifang Jia & Bing Ren & Tao Pan & Chuan He, 2014. "N6-methyladenosine-dependent regulation of messenger RNA stability," Nature, Nature, vol. 505(7481), pages 117-120, January.
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