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

Area of Science:

• Biochemistry
• Molecular Biology
• Radiation Biology

Background:

• Effective radiation triage and biological dosimetry are crucial for managing individuals exposed during radiological incidents.
• Assessing radiation dose accurately is vital for timely medical intervention and treatment planning.

Purpose of the Study:

• To identify novel RNA biomarkers for radiation exposure using genome-wide screening of N6-methyladenosine (m⁶A) modifications.
• To evaluate the potential of specific m⁶A-modified mRNAs as biodosimeters for radiation dose estimation.

Main Methods:

• Genome-wide screening of messenger RNAs (mRNAs) with altered N6-methyladenosine (m⁶A) levels post-irradiation.
• Analysis of m⁶A levels of Ncoa4, Ate1, and Fgf22 in mouse peripheral blood mononuclear cells (PBMCs).
• Validation of Ncoa4 m⁶A as a radiation biomarker in mice, monkeys, humans, and cancer patients undergoing radiation therapy.

Main Results:

• The m⁶A levels of Ncoa4, Ate1, and Fgf22 in mouse PBMCs exhibited significant dose-response relationships after irradiation.
• Ncoa4 RNA m⁶A modification demonstrated radiation specificity, cross-species conservation (mice, monkeys, humans), and prolonged detection up to 28 days post-exposure.
• Biodosimetric models based on Ncoa4 m⁶A were successfully constructed for estimating absorbed radiation doses.

Conclusions:

• RNA m⁶A modifications, particularly Ncoa4, show significant potential as sensitive and specific biomarkers for radiation biodosimetry.
• These findings support the clinical application of RNA m⁶A in managing radiation accidents and optimizing cancer radiation therapy.
• The study highlights the feasibility of utilizing RNA m⁶A for rapid and accurate radiation dose assessment in diverse settings.