Department of Biomedical Sciences, Parkinson's Disorder Research Program, Iowa State University, Ames, Iowa 50011.
Toxicol Sci. 2021 Apr 27;181(1):13-22. doi: 10.1093/toxsci/kfab021.
Epitranscriptomics, the study of chemically modified RNAs, is a burgeoning field being explored in a variety of scientific disciplines. Of the currently known epitranscriptomic modifications, N6-methyladenosine (m6A) methylation is the most abundant. The m6A modification is predominantly regulated by 3 tiers of protein modulators classified as writers, erasers, and readers. Depending upon cellular needs, these proteins function to deposit, remove, or read the methyl modifications on cognate mRNAs. Many environmental chemicals including heavy metals, pesticides, and other toxic pollutants, are all known to perturb transcription and translation machinery to exert their toxic responses. As such, we herein review how the m6A modification may be affected under different toxicological paradigms. Furthermore, we discuss how toxicants can affect the 3 tiers of regulation directly, and how these effects influence the m6A-modified mRNAs. Lastly, we highlight the disparities between published findings and theories, especially those concerning the m6A reader tier of regulation. In the far-reaching field of toxicology, m6A epitranscriptomics provides another enticing avenue to explore new mechanisms and therapies for a diverse range of environmentally linked disorders and diseases.
表观转录组学是研究 RNA 化学修饰的一门新兴学科，目前已经在多个科学领域得到了广泛的研究。在已知的表观转录组修饰中，N6-甲基腺苷（m6A）甲基化修饰最为丰富。m6A 修饰主要由 3 层蛋白调节剂调控，分为写入器、擦除器和读取器。根据细胞的需要，这些蛋白可以在同源的 mRNA 上沉积、去除或读取甲基化修饰。许多环境化学物质，包括重金属、农药和其他有毒污染物，都已知会扰乱转录和翻译机制，从而发挥其毒性作用。因此，我们在此综述了 m6A 修饰在不同毒理学模型下可能受到的影响。此外，我们还讨论了毒物如何直接影响调控的 3 个层次，以及这些影响如何影响 m6A 修饰的 mRNA。最后，我们强调了已发表的研究结果和理论之间的差异，特别是关于 m6A 阅读器调控层次的差异。在广泛的毒理学领域中，m6A 表观转录组学为研究与环境相关的各种疾病和障碍的新机制和治疗方法提供了另一个诱人的途径。
