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

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.