RNA damage and its implications in genome stability

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2025-03-01 DOI:10.1016/j.dnarep.2025.103821

Mustapha Olatunji , Yuan Liu

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引用次数: 0

Abstract

Endogenous and environmental stressors can damage DNA and RNA to compromise genome and transcriptome stability and integrity in cells, leading to genetic instability and diseases. Recent studies have demonstrated that RNA damage can also modulate genome stability via RNA-templated DNA synthesis, suggesting that it is essential to maintain RNA integrity for the sustainment of genome stability. However, little is known about RNA damage and repair and their roles in modulating genome stability. Current efforts have mainly focused on revealing RNA surveillance pathways that detect and degrade damaged RNA, while the critical role of RNA repair is often overlooked. Due to their abundance and susceptibility to nucleobase damaging agents, it is essential for cells to evolve robust RNA repair mechanisms that can remove RNA damage, maintaining RNA integrity during gene transcription. This is supported by the discovery of the alkylated RNA nucleobase repair enzyme human AlkB homolog 3 that can directly remove the methyl group on damaged RNA nucleobases, predominantly in the nucleus of human cells, thereby restoring the integrity of the damaged RNA nucleobases. This is further supported by the fact that several DNA repair enzymes can also process RNA damage. In this review, we discuss RNA damage and its effects on cellular function, DNA repair, genome instability, and potential RNA damage repair mechanisms. Our review underscores the necessity for future research on RNA damage and repair and their essential roles in modulating genome stability.

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RNA损伤及其对基因组稳定性的影响

内源性和环境压力源可破坏DNA和RNA，损害细胞中基因组和转录组的稳定性和完整性，导致遗传不稳定和疾病。最近的研究表明，RNA损伤也可以通过RNA模板DNA合成来调节基因组的稳定性，这表明维持RNA的完整性对于维持基因组的稳定性至关重要。然而，人们对RNA损伤和修复及其在调节基因组稳定性中的作用知之甚少。目前的努力主要集中在揭示RNA监测途径，检测和降解受损的RNA，而RNA修复的关键作用往往被忽视。由于它们的丰度和对核碱基损伤剂的易感性，细胞必须进化出强大的RNA修复机制，以消除RNA损伤，在基因转录过程中保持RNA的完整性。烷基化RNA核碱基修复酶human AlkB homolog 3的发现支持了这一点，它可以直接去除受损RNA核碱基上的甲基，主要是在人类细胞核中，从而恢复受损RNA核碱基的完整性。一些DNA修复酶也可以处理RNA损伤，这一事实进一步支持了这一观点。在这篇综述中，我们讨论了RNA损伤及其对细胞功能的影响、DNA修复、基因组不稳定性以及潜在的RNA损伤修复机制。我们的综述强调了未来研究RNA损伤和修复及其在调节基因组稳定性中的重要作用的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.