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RNA METABOLISM

A-to-I editing prevents self-RNA sensing

Nature Reviews Molecular Cell Biology volume 24, page 85 (2023)Cite this article

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Sensing and discriminating self from non-self nucleic acids is key to reliably initiating antiviral responses. In vertebrates, the principle of discriminating self from non-self nucleic-acid ligands is based on their availability, cellular localization, conformation, modification, and on structural and/or sequence motifs. RNA species such as viral double-stranded RNA (dsRNA) can activate cytosolic RNA sensors and trigger innate immunity.

A landmark 2015 study by Liddicoat et al. reported that adenosine-to-inosine (A-to-I) editing of endogenous dsRNA is the vital function of adenosine deaminases acting on RNA 1 (ADAR1). The study proposed that A-to-I editing marks endogenous dsRNA structures as self by altering Watson–Crick A–U base pairs to the weaker I.U wobble base pairs, which destabilizes dsRNA and prevents its sensing by the MDA5–MAVS pathway, which triggers interferon responses. In retrospect, one should also appreciate the pioneering work published in 1988 by Bass and Weintraub, which first suggested that ADAR1 unwinds and destabilizes dsRNA. Since then, our knowledge of how A-to-I editing serves as an immune tolerance mechanism and affects human health has rapidly increased.

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References

Original article

  • Liddicoat, B. J. et al. RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science 349, 1115–1120 (2015)

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Related article

  • Bass, B. L. & Weintraub, H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55, 1089–1098 (1988)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Leilei Chen

  2. NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Leilei Chen

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  1. Leilei Chen
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Correspondence to Leilei Chen.

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Cite this article

Chen, L. A-to-I editing prevents self-RNA sensing. Nat Rev Mol Cell Biol 24, 85 (2023). https://doi.org/10.1038/s41580-022-00540-4

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  • DOI: https://doi.org/10.1038/s41580-022-00540-4

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