Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
Institute of Molecular Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria; Institute of Medical Genetics, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
Ageing Res Rev. 2022 Nov;81:101700. doi: 10.1016/j.arr.2022.101700. Epub 2022 Jul 28.
Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just beginning to be studied in the context of ageing and stress resistance. RNA modifications modulate gene expression by affecting translation initiation and speed, miRNA binding, RNA stability, and RNA degradation. Nonetheless, the precise underlying molecular mechanisms and physiological consequences of most alterations of the epitranscriptome are still only poorly understood. We here systematically review different types of modifications of rRNA, tRNA and mRNA, the methodology to analyze them, current challenges in the field, and human disease associations. Furthermore, we compiled evidence for a connection between individual enzymes, which install RNA modifications, and lifespan in yeast, worm and fly. We also included resistance to different stressors and competitive fitness as search criteria for genes potentially relevant to ageing. Promising candidates identified by this approach include RCM1/NSUN5, RRP8, and F33A8.4/ZCCHC4 that introduce base methylations in rRNA, the methyltransferases DNMT2 and TRM9/ALKBH8, as well as factors involved in the thiolation or A to I editing in tRNA, and finally the mA machinery for mRNA.
RNA 的修饰统称为“转录后组”，可能为衰老科学中的干预措施提供新的生物标志物和创新靶点，但它们在衰老和抗应激方面的研究才刚刚开始。RNA 修饰通过影响翻译起始和速度、miRNA 结合、RNA 稳定性和 RNA 降解来调节基因表达。尽管如此，大多数转录后组修饰的精确潜在分子机制和生理后果仍知之甚少。我们在这里系统地综述了 rRNA、tRNA 和 mRNA 的不同类型修饰、分析它们的方法、该领域的当前挑战以及与人类疾病的关联。此外，我们还为酵母、蠕虫和苍蝇中单个酶与寿命之间的联系提供了证据，这些酶可修饰 RNA 。我们还将抵抗不同胁迫和竞争适应能力作为与衰老相关的潜在基因的搜索标准。通过这种方法确定的有前途的候选基因包括在 rRNA 中引入碱基甲基化的 RCM1/NSUN5、RRP8 和 F33A8.4/ZCCHC4，甲基转移酶 DNMT2 和 TRM9/ALKBH8，以及参与 tRNA 硫代或 A 到 I 编辑的因子，最后是 mRNA 的 mA 机制。
