Tanaka Mikiei, Chock P Boon
Biochemistry and Biophysics Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.
Front Mol Biosci. 2021 May 12;8:685331. doi: 10.3389/fmolb.2021.685331. eCollection 2021.
Elevated level of oxidized RNA was detected in vulnerable neurons in Alzheimer patients. Subsequently, several diseases and pathological conditions were reported to be associated with RNA oxidation. In addition to several oxidized derivatives, cross-linking and unique strand breaks are generated by RNA oxidation. With a premise that dysfunctional RNA mediated by oxidation is the pathogenetic molecular mechanism, intensive investigations have revealed the mechanism for translation errors, including premature termination, which gives rise to aberrant polypeptides. To this end, we and others revealed that mRNA oxidation could compromise its translational activity and fidelity. Under certain conditions, oxidized RNA can also induce several signaling pathways, to mediate inflammatory response and induce apoptosis. In this review, we focus on the oxidative modification of RNA and its resulting effect on protein synthesis as well as cell signaling. In addition, we will also discuss the potential roles of enzymatic oxidative modification of RNA in mediating cellular effects.
在阿尔茨海默病患者的易损神经元中检测到氧化RNA水平升高。随后，有报道称几种疾病和病理状况与RNA氧化有关。除了几种氧化衍生物外，RNA氧化还会产生交联和独特的链断裂。基于氧化介导的功能失调RNA是致病分子机制这一前提，深入研究揭示了翻译错误的机制，包括导致异常多肽的提前终止。为此，我们和其他人发现mRNA氧化会损害其翻译活性和保真度。在某些条件下，氧化RNA还可以诱导多种信号通路，介导炎症反应并诱导细胞凋亡。在这篇综述中，我们重点关注RNA的氧化修饰及其对蛋白质合成以及细胞信号传导的影响。此外，我们还将讨论RNA的酶促氧化修饰在介导细胞效应中的潜在作用。
