Department of Chemistry and the RNA Institute, College of Arts and Science, University at Albany, State University of New York , Albany, NY, USA.
Institute of Biosciences and Technology, Texas A&M University , Houston, TX, USA.
RNA Biol. 2020 Nov;17(11):1560-1575. doi: 10.1080/15476286.2020.1722449. Epub 2020 Feb 7.
RNA plays essential roles in not only translating nucleic acids into proteins, but also in gene regulation, environmental interactions and many human diseases. Nature uses over 150 chemical modifications to decorate RNA and diversify its functions. With the fast-growing RNA research in the burgeoning field of 'epitranscriptome', a term describes post-transcriptional RNA modifications that can dynamically change the transcriptome, it becomes clear that these modifications participate in modulating gene expression and controlling the cell fate, thereby igniting the new interests in RNA-based drug discovery. The dynamics of these RNA chemical modifications is orchestrated by coordinated actions of an array of writer, reader and eraser proteins. Deregulated expression of these RNA modifying proteins can lead to many human diseases including cancer. In this review, we highlight several critical modifications, namely mA, mA, mC, inosine and pseudouridine, in both coding and non-coding RNAs. In parallel, we present a few other cancer-related tRNA and rRNA modifications. We further discuss their roles in cancer promotion or tumour suppression. Understanding the molecular mechanisms underlying the biogenesis and turnover of these RNA modifications will be of great significance in the design and development of novel anticancer drugs.
RNA 在将核酸翻译成蛋白质方面发挥着重要作用，同时也在基因调控、环境相互作用和许多人类疾病中发挥着重要作用。自然界利用超过 150 种化学修饰来修饰 RNA，使其功能多样化。随着“转录后组学”这一新兴领域中 RNA 研究的快速发展，人们清楚地认识到这些修饰可以动态改变转录组，参与调节基因表达和控制细胞命运，从而激发了基于 RNA 的新药发现的新兴趣。这些 RNA 化学修饰的动态由一系列 Writer、Reader 和 Eraser 蛋白的协调作用来调控。这些 RNA 修饰蛋白的表达失调可导致许多人类疾病，包括癌症。在这篇综述中，我们重点介绍了编码和非编码 RNA 中的几种关键修饰，即 mA、m 6 A、m 5 C、肌苷和假尿嘧啶。同时，我们还介绍了其他几种与癌症相关的 tRNA 和 rRNA 修饰。我们进一步讨论了它们在促进癌症或抑制肿瘤方面的作用。了解这些 RNA 修饰的生物发生和周转的分子机制对于设计和开发新型抗癌药物具有重要意义。
