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

Chen, Hongxia; Zhao, Xi; Yang, Wei; Zhang, Qi; Hao, Rongjiao; Jiang, Siao; Han, Huihui; Yu, Zuyin et al. · Nat Commun · 2023

basic_science · Level V

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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 (m<sup>6</sup>A) levels showed significant alteration after acute irradiation. The m<sup>6</sup>A 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 m<sup>6</sup>A 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 m<sup>6</sup>A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m<sup>6</sup>A in radiation accidents management and clinical applications.

Medical subject headings