Vu Minh-Anh, Spagnuolo Manuela, Chen Chun-Long
Institut Curie, PSL Research University, CNRS UMR3244, Dynamics of Genetic Information, Sorbonne Université, 75005 Paris, France.
NAR Cancer. 2025 Aug 11;7(3):zcaf022. doi: 10.1093/narcan/zcaf022. eCollection 2025 Sep.
R-loops or DNA-RNA hybrids are prominent nucleic acid structures that commonly arise during transcription. These structures play important biological functions, such as regulating gene expression and DNA repair. However, when unresolved by nucleic acid processing factors, pathological R-loops can be harmful and lead to genome instability. -Methyladenosine (m6A), the most prevalent modification in messenger RNA, has been recently identified to be crucial for regulating R-loop balance and maintaining genome stability. Strikingly, m6A-modified R-loop formation can have opposing consequences, either stabilization or resolution, depending on the biological context. In this review, we discuss the current knowledge of the regulatory roles of m6A on R-loops across various processes, including gene transcription, DNA repair, and centromere and telomere stability. Additionally, we explore other m6A-mediated processes, such as nascent transcription and chromatin landscape, that potentially affect R-loop dynamics. Finally, we discuss the current limitations and future directions of studying the m6A-R-loop axis, as well as the opportunities to target this pathway as a potential therapeutic strategy.
R环或DNA - RNA杂交体是转录过程中常见的重要核酸结构。这些结构发挥着重要的生物学功能，如调节基因表达和DNA修复。然而，当核酸加工因子无法解决时，病理性R环可能有害并导致基因组不稳定。N6 - 甲基腺苷（m6A）是信使RNA中最普遍的修饰，最近已被确定对调节R环平衡和维持基因组稳定性至关重要。引人注目的是，m6A修饰的R环形成可能会产生相反的结果，即稳定或分解，这取决于生物学背景。在这篇综述中，我们讨论了目前关于m6A在包括基因转录、DNA修复以及着丝粒和端粒稳定性等各种过程中对R环的调控作用的认识。此外，我们还探讨了其他可能影响R环动态的m6A介导的过程，如新生转录和染色质景观。最后，我们讨论了研究m6A - R环轴目前的局限性和未来方向，以及将该途径作为潜在治疗策略的靶向机会。
