Communications Biology (May 2024)

The implications of APOBEC3-mediated C-to-U RNA editing for human disease

  • Melissa Van Norden,
  • Zackary Falls,
  • Sapan Mandloi,
  • Brahm H. Segal,
  • Bora E. Baysal,
  • Ram Samudrala,
  • Peter L. Elkin

DOI
https://doi.org/10.1038/s42003-024-06239-w
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 10

Abstract

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Abstract Intra-organism biodiversity is thought to arise from epigenetic modification of constituent genes and post-translational modifications of translated proteins. Here, we show that post-transcriptional modifications, like RNA editing, may also contribute. RNA editing enzymes APOBEC3A and APOBEC3G catalyze the deamination of cytosine to uracil. RNAsee (RNA site editing evaluation) is a computational tool developed to predict the cytosines edited by these enzymes. We find that 4.5% of non-synonymous DNA single nucleotide polymorphisms that result in cytosine to uracil changes in RNA are probable sites for APOBEC3A/G RNA editing; the variant proteins created by such polymorphisms may also result from transient RNA editing. These polymorphisms are associated with over 20% of Medical Subject Headings across ten categories of disease, including nutritional and metabolic, neoplastic, cardiovascular, and nervous system diseases. Because RNA editing is transient and not organism-wide, future work is necessary to confirm the extent and effects of such editing in humans.