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

• Published in: Communications biology Vol. 7; no. 1; pp. 529 - 10
• Main Authors: Van Norden, Melissa, Falls, Zackary, Mandloi, Sapan, Segal, Brahm H., Baysal, Bora E., Samudrala, Ram, Elkin, Peter L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.05.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 45/70; 45/91; 631/114/2413; 692/4017; APOBEC Deaminases; APOBEC-3G Deaminase - genetics; APOBEC-3G Deaminase - metabolism; Biodiversity; Biomedical and Life Sciences; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Cytosine; Cytosine - metabolism; Cytosine Deaminase - genetics; Cytosine Deaminase - metabolism; Deamination; Editing; Enzymes; Epigenetics; Humans; Life Sciences; Nervous system; Nervous system diseases; Polymorphism, Single Nucleotide; Post-transcription; Post-translation; Proteins - genetics; Proteins - metabolism; RNA Editing; Single-nucleotide polymorphism; Uracil; Uracil - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06239-w

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. A survey of known human DNA editing sites with an RNA editing site prediction algorithm suggests APOBEC-mediated RNA editing may produce some of the same protein variants, with the possibility of affecting multiple areas of health.