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Annual Review of Pathology: Mechanisms of Disease

Volume 20, 2025

RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease

  • Hani S. Zaher1 and Nima Mosammaparast2
  • 1Department of Biology, Washington University in St. Louis, St. Louis, Missouri, USA; email: [email protected] 2Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA; email: [email protected]
  • Vol. 20:433-457 (Volume publication date January 2025)
  • First published as a Review in Advance on October 30, 2024
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

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.

Keyword(s): alkylation, DNA repair, oxidation, ribosome, RNA damage, RNA quality control, spliceosome
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2025-01-24
2025-06-22
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/content/journals/10.1146/annurev-pathmechdis-111523-023516
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RNA Damage Responses in Cellular Homeostasis, Genome Stability, and Disease
Annual Review of Pathology: Mechanisms of Disease 20, 433 (2025); https://doi.org/10.1146/annurev-pathmechdis-111523-023516
/content/journals/10.1146/annurev-pathmechdis-111523-023516
/content/journals/10.1146/annurev-pathmechdis-111523-023516
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