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RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation

Author

Listed:
  • Hongxia Chen

    (Beijing Institute of Radiation Medicine)

  • Xi Zhao

    (Beijing Institute of Radiation Medicine)

  • Wei Yang

    (the First Medical Center of Chinese PLA General Hospital)

  • Qi Zhang

    (Beijing Institute of Radiation Medicine
    University of South China)

  • Rongjiao Hao

    (Beijing Institute of Radiation Medicine
    University of Hebei)

  • Siao Jiang

    (Beijing Institute of Radiation Medicine
    University of Hebei)

  • Huihui Han

    (Beijing Institute of Radiation Medicine)

  • Zuyin Yu

    (Beijing Institute of Radiation Medicine)

  • Shuang Xing

    (Beijing Institute of Radiation Medicine)

  • Changjiang Feng

    (the First Medical Center of Chinese PLA General Hospital)

  • Qianqian Wang

    (the First Medical Center of Chinese PLA General Hospital)

  • Hao Lu

    (Beijing Institute of Radiation Medicine)

  • Yuanfeng Li

    (Beijing Institute of Radiation Medicine)

  • Cheng Quan

    (Beijing Institute of Radiation Medicine)

  • Yiming Lu

    (Beijing Institute of Radiation Medicine
    University of Hebei)

  • Gangqiao Zhou

    (Beijing Institute of Radiation Medicine
    University of South China
    University of Hebei
    Nanjing Medical University)

Abstract

Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.

Suggested Citation

  • Hongxia Chen & Xi Zhao & Wei Yang & Qi Zhang & Rongjiao Hao & Siao Jiang & Huihui Han & Zuyin Yu & Shuang Xing & Changjiang Feng & Qianqian Wang & Hao Lu & Yuanfeng Li & Cheng Quan & Yiming Lu & Gangq, 2023. "RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42665-w
    DOI: 10.1038/s41467-023-42665-w
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    References listed on IDEAS

    as
    1. Yang Xiang & Benoit Laurent & Chih-Hung Hsu & Sigrid Nachtergaele & Zhike Lu & Wanqiang Sheng & Chuanyun Xu & Hao Chen & Jian Ouyang & Siqing Wang & Dominic Ling & Pang-Hung Hsu & Lee Zou & Ashwini Ja, 2017. "Correction: Corrigendum: RNA m6A methylation regulates the ultraviolet-induced DNA damage response," Nature, Nature, vol. 552(7685), pages 430-430, December.
    2. Yang Xiang & Benoit Laurent & Chih-Hung Hsu & Sigrid Nachtergaele & Zhike Lu & Wanqiang Sheng & Chuanyun Xu & Hao Chen & Jian Ouyang & Siqing Wang & Dominic Ling & Pang-Hung Hsu & Lee Zou & Ashwini Ja, 2017. "RNA m6A methylation regulates the ultraviolet-induced DNA damage response," Nature, Nature, vol. 543(7646), pages 573-576, March.
    3. Verna Van & Janae B. Brown & Corin R. O’Shea & Hannah Rosenbach & Ijaz Mohamed & Nna-Emeka Ejimogu & Toan S. Bui & Veronika A. Szalai & Kelly N. Chacón & Ingrid Span & Fangliang Zhang & Aaron T. Smith, 2023. "Iron-sulfur clusters are involved in post-translational arginylation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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