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

• Published in: Nature communications Vol. 14; no. 1; p. 6912
• Main Authors: Chen, Hongxia, Zhao, Xi, Yang, Wei, Zhang, Qi, Hao, Rongjiao, Jiang, Siao, Han, Huihui, Yu, Zuyin, Xing, Shuang, Feng, Changjiang, Wang, Qianqian, Lu, Hao, Li, Yuanfeng, Quan, Cheng, Lu, Yiming, Zhou, Gangqiao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-10-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 49/61; 631/208; 692/53; 692/53/2421; 692/700/3160; Accidents; Biomarkers; Blood cells; Dose-response effects; Dosimeters; Dosimetry; Estimation; Feasibility studies; Genes; Genomes; Humanities and Social Sciences; Ionizing radiation; Irradiation; Leukocytes (mononuclear); multidisciplinary; N6-methyladenosine; Peripheral blood mononuclear cells; Radiation; Radiation dosage; Radiation dosimetry; Radiation effects; Radiation therapy; Ribonucleic acid; RNA; RNA modification; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-42665-w

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
6
A) levels showed significant alteration after acute irradiation. The m
6
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
6
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
6
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
6
A in radiation accidents management and clinical applications.
Radiation dosimetry are critical for the medical management of individuals exposed to ionizing radiation (IR). Here, authors show that the RNA m6A levels of Ncoa4, Ate1 and Fgf22 genes in peripheral blood cells could serve as dosimetry of IR exposure.