Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure.
Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure.
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循环 tRNA 衍生的小 RNA 作为重离子、质子和 X 射线暴露的新型辐射生物标志物
DOI：
10.3390/ijms222413476
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发表时间：
2021-12-15
影响因子：
5.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wei W;Bai H;Chen Y;Zhang T;Zhang Y;Hua J;He J;Ding N;Zhou H;Wang J
有效和微创的辐射生物标志物在核事故或空间任务中的暴露场景中是有价值的。近年来的研究开辟了循环小非编码RNA（sncRNA）作为辐射生物标志物的新视野。tRNA衍生的小RNA（tRNA-derived small RNA，tsRNA）是一类新的sncRNA。它在细胞外囊泡或血液中比其他类型的sncRNA更丰富，作为有前途的生物标志物具有巨大潜力。然而，循环中的tsRNA响应于电离辐射尚未报道。本研究以昆明种小鼠为研究对象，分别给予0.05 ~ 2戈伊的碳离子、质子或X射线全身照射，通过RNA测序技术检测小鼠血清中sncRNA的表达。经过条件筛选和验证，我们首次鉴定出5种tsRNA，其中包括4种tRNA相关片段（tRFs）和1种tRNA半片段（tiRNA），它们在3种辐射照射后水平均显著下降。此外，这5个血清tsRNA的辐射反应在其他品系小鼠中重现，并且它们的序列可以在人血清中检测到。此外，我们开发了基于tsRNA生物标志物的多因素模型，以高灵敏度和特异性指示辐射暴露程度。这些发现表明，循环中的tsRNA可以作为新的微创生物标志物，并可以在暴露情况下4小时内从血液样本采集中进行分类或剂量评估。
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.
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