Zaher Hani S, Mosammaparast Nima
Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA; email:
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA; email:
Annu Rev Pathol. 2025 Jan;20(1):433-457. doi: 10.1146/annurev-pathmechdis-111523-023516. Epub 2025 Jan 2.
All cells are exposed to chemicals that can damage their nucleic acids. Cells must protect these polymers because they code for key factors or complexes essential for life. Much of the work on nucleic acid damage has naturally focused on DNA, partly due to the connection between mutagenesis and human disease, especially cancer. Recent work has shed light on the importance of RNA damage, which triggers a host of conserved RNA quality control mechanisms. Because many RNA species are transient, and because of their ability to be retranscribed, RNA damage has largely been ignored. Yet, because of the connection between damaged RNA and DNA during transcription, and the association between essential complexes that process or decode RNAs, notably spliceosomes and ribosomes, the appropriate handling of damaged RNAs is critical for maintaining cellular homeostasis. This notion is bolstered by disease states, including neurodevelopmental and neurodegenerative diseases, that may arise upon loss or misregulation of RNA quality control mechanisms.
所有细胞都会接触到可能损害其核酸的化学物质。细胞必须保护这些聚合物，因为它们编码生命所必需的关键因子或复合物。核酸损伤方面的许多研究自然都集中在DNA上，部分原因是诱变与人类疾病尤其是癌症之间的联系。最近的研究揭示了RNA损伤的重要性，RNA损伤会触发一系列保守的RNA质量控制机制。由于许多RNA种类是短暂存在的，并且由于它们能够被重新转录，RNA损伤在很大程度上被忽视了。然而，由于转录过程中受损RNA与DNA之间的联系，以及处理或解码RNA的重要复合物（特别是剪接体和核糖体）之间的关联，正确处理受损RNA对于维持细胞内稳态至关重要。包括神经发育和神经退行性疾病在内的疾病状态可能因RNA质量控制机制的丧失或失调而出现，这一观点得到了支持。
