RNA 修饰在基因组完整性中的新兴作用。
Emerging roles of RNA modifications in genome integrity.
机构信息
Miller laboratory at the University of Texas at Austin.
Livestrong Cancer Institutes.
出版信息
Brief Funct Genomics. 2021 Mar 27;20(2):106-112. doi: 10.1093/bfgp/elaa022.
Post-translational modifications of proteins are well-established participants in DNA damage response (DDR) pathways, which function in the maintenance of genome integrity. Emerging evidence is starting to reveal the involvement of modifications on RNA in the DDR. RNA modifications are known regulators of gene expression but how and if they participate in DNA repair and genome maintenance has been poorly understood. Here, we review several studies that have now established RNA modifications as key components of DNA damage responses. RNA modifying enzymes and the binding proteins that recognize these modifications localize to and participate in the repair of UV-induced and DNA double-strand break lesions. RNA modifications have a profound effect on DNA-RNA hybrids (R-loops) at DNA damage sites, a structure known to be involved in DNA repair and genome stability. Given the importance of the DDR in suppressing mutations and human diseases such as neurodegeneration, immunodeficiencies, cancer and aging, RNA modification pathways may be involved in human diseases not solely through their roles in gene expression but also by their ability to impact DNA repair and genome stability.
蛋白质的翻译后修饰是 DNA 损伤反应 (DDR) 途径中的重要参与者，该途径在维持基因组完整性方面发挥作用。新出现的证据开始揭示 RNA 修饰在 DDR 中的作用。RNA 修饰是已知的基因表达调节剂，但它们如何以及是否参与 DNA 修复和基因组维持仍知之甚少。在这里，我们回顾了一些现已确立 RNA 修饰作为 DNA 损伤反应关键组成部分的研究。RNA 修饰酶以及识别这些修饰的结合蛋白定位于 UV 诱导和 DNA 双链断裂损伤的修复，并参与其中。RNA 修饰对 DNA 损伤部位的 DNA-RNA 杂交 (R 环) 有深远影响，该结构已知参与 DNA 修复和基因组稳定性。鉴于 DDR 在抑制突变和人类疾病（如神经退行性疾病、免疫缺陷、癌症和衰老）方面的重要性，RNA 修饰途径可能不仅通过其在基因表达中的作用，而且通过其影响 DNA 修复和基因组稳定性的能力，参与人类疾病。
Zotero 插件