Abstract
The effective and minimally invasive radiation biomarkers are valuable for exposure scenarios in nuclear accidents or space missions. Recent studies have opened the new sight of circulating small non-coding RNA (sncRNA) as radiation biomarkers. The tRNA-derived small RNA (tsRNA) is a new class of sncRNA. It is more abundant than other kinds of sncRNAs in extracellular vesicles or blood, presenting great potential as promising biomarkers. However, the circulating tsRNAs in response to ionizing radiation have not been reported. In this research, Kunming mice were total-body exposed to 0.05–2 Gy of carbon ions, protons, or X-rays, and the RNA sequencing was performed to profile the expression of sncRNAs in serum. After conditional screening and validation, we firstly identified 5 tsRNAs including 4 tRNA-related fragments (tRFs) and 1 tRNA half (tiRNA) which showed a significant level decrease after exposure to three kinds of radiations. Moreover, the radiation responses of these 5 serum tsRNAs were reproduced in other mouse strains, and the sequences of them could be detected in serum of humans. Furthermore, we developed multi-factor models based on tsRNA biomarkers to indicate the degree of radiation exposure with high sensitivity and specificity. These findings suggest that the circulating tsRNAs can serve as new minimally invasive biomarkers and can make a triage or dose assessment from blood sample collection within 4 h in exposure scenarios.
Highlights
Ionizing radiation from nuclear accidents, outer space, or radiation facilities is a major concern for human health
Over 75% of small non-coding RNA (sncRNA) reads were from the mature tRNAs, 1% of reads were from pre-tRNAs or miRNAs in all dose groups (Figure 1B)
It was found that most of tRNA-derived small RNA (tsRNA) were classified as tRNA-related fragments (tRFs)-5c, while only 3–6% of the fragments were classified as tiRNA (Figure 1C)
Summary
Ionizing radiation from nuclear accidents, outer space, or radiation facilities is a major concern for human health. The widely used physical dosimeters have limitations in indicating the individual responses because the biological effects may be different between different individuals [1]. Radiation-responsive biomarkers can indicate the individual absorbed dose and provide information about radiation-induced biological damage. The promising radiation biomarkers are valuable for personalized assessment in exposure scenarios, especially for low doses of radiation exposure which cause mild symptoms or cancer risk by a progressive pattern. The detection processes of these biomarkers are time-consuming and complex [5,6]. These considerable limitations make an urgent demand for new rapid detection and minimally invasive biomarkers
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