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环境暴露、表观转录组扰动与人类疾病

Environmental Exposure, Epitranscriptomic Perturbations, and Human Diseases.

作者信息

Wei Songbo, Tao Huan-Yu, Duan Zheng, Wang Yinsheng

机构信息

Department of Chemistry, University of California, Riverside, California 92521-0403, United States.

出版信息

Environ Sci Technol. 2025 Apr 8;59(13):6387-6399. doi: 10.1021/acs.est.5c00907. Epub 2025 Mar 24.

Abstract

Epitranscriptomics is a rapidly evolving field, and it examines how chemical modifications on RNA regulate gene expression. Increasing lines of evidence support that exposure to various environmental agents can change substantially chemical modifications on RNA, thereby perturbing gene expression and contributing to disease development in humans. However, the molecular mechanisms through which environmental exposure impairs RNA modification-associated proteins ("reader", "writer", and "eraser" or RWE proteins) and alters the landscape of RNA modifications remain poorly understood. Here, we provide our perspectives on the current knowledge about how environmental exposure alters the epitranscriptome, where we focus on dynamic changes in RNA modifications and their regulatory proteins elicited by exposure to environmental agents. We discuss how these epitranscriptomic alterations may contribute to the development of human diseases, especially neurodegeneration and cancer. We also discuss the potential and technical challenges of harnessing RNA modifications as biomarkers for monitoring environmental exposure. Finally, we emphasize the need to integrate multiomics approaches to decipher the complex interplay between environmental exposure and the epitranscriptome and offer a forward-looking viewpoint on future research priorities that may inform public health interventions and environmental regulations.

摘要

表观转录组学是一个快速发展的领域,它研究RNA上的化学修饰如何调节基因表达。越来越多的证据支持,暴露于各种环境因素会显著改变RNA上的化学修饰,从而扰乱基因表达并导致人类疾病的发展。然而,环境暴露损害RNA修饰相关蛋白(“读取器”、“写入器”和“擦除器”或RWE蛋白)并改变RNA修饰格局的分子机制仍知之甚少。在这里,我们就环境暴露如何改变表观转录组的现有知识发表我们的观点,我们关注的是暴露于环境因素引起的RNA修饰及其调节蛋白的动态变化。我们讨论了这些表观转录组改变如何可能导致人类疾病的发展,特别是神经退行性变和癌症。我们还讨论了利用RNA修饰作为监测环境暴露生物标志物的潜力和技术挑战。最后,我们强调需要整合多组学方法来破译环境暴露与表观转录组之间的复杂相互作用,并对未来的研究重点提供前瞻性观点,这可能为公共卫生干预和环境法规提供参考。

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