Epitranscriptome in action: RNA modifications in the DNA damage response

IF 14.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Cell Pub Date : 2024-10-03 DOI:10.1016/j.molcel.2024.09.003
Blerta Xhemalçe, Kyle M. Miller, Natalia Gromak
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Abstract

Complex pathways involving the DNA damage response (DDR) contend with cell-intrinsic and -extrinsic sources of DNA damage. DDR mis-regulation results in genome instability that can contribute to aging and diseases including cancer and neurodegeneration. Recent studies have highlighted key roles for several RNA species in the DDR, including short RNAs and RNA/DNA hybrids (R-loops) at DNA break sites, all contributing to efficient DNA repair. RNAs can undergo more than 170 distinct chemical modifications. These RNA modifications have emerged as key orchestrators of the DDR. Here, we highlight the function of enzyme- and non-enzyme-induced RNA modifications in the DDR, with particular emphasis on m6A, m5C, and RNA editing. We also discuss stress-induced RNA damage, including RNA alkylation/oxidation, RNA-protein crosslinks, and UV-induced RNA damage. Uncovering molecular mechanisms that underpin the contribution of RNA modifications to DDR and genome stability will have direct application to disease and approaches for therapeutic intervention.
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Epitranscriptome in action:DNA 损伤反应中的 RNA 修饰
涉及 DNA 损伤应答(DDR)的复杂通路要与细胞内在和外在的 DNA 损伤源进行抗争。DDR 失调会导致基因组不稳定,从而引起衰老以及癌症和神经变性等疾病。最近的研究强调了几种 RNA 在 DDR 中的关键作用,包括 DNA 断裂位点的短 RNA 和 RNA/DNA 杂交(R-环),它们都有助于高效的 DNA 修复。RNA 可进行 170 多种不同的化学修饰。这些 RNA 修饰已成为 DDR 的关键协调者。在此,我们将重点介绍酶和非酶诱导的 RNA 修饰在 DDR 中的功能,特别强调 m6A、m5C 和 RNA 编辑。我们还讨论了应激诱导的 RNA 损伤,包括 RNA 烷基化/氧化、RNA 蛋白交联和紫外线诱导的 RNA 损伤。揭示 RNA 修饰对 DDR 和基因组稳定性所起作用的分子机制将直接应用于疾病和治疗干预方法。
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来源期刊
Molecular Cell
Molecular Cell 生物-生化与分子生物学
CiteScore
26.00
自引率
3.80%
发文量
389
审稿时长
1 months
期刊介绍: Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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