The Implications of APOBEC3-Mediated C-to-U RNA Editing for Human Disease

We are publishing a manuscript which shows a connection between climate change and other environmental factors including pandemics and our gene expression. This manuscript also demonstrates the importance of RNA editing in the understanding of molecular biology.

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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.

Classically, our biodiversity is thought to come from our constitutive genetics, epigenetic phenomenon, transcriptional differences, and post-translational modification of proteins. Here, we have shown evidence that RNA editing could also play a role in creating the variant proteins that contribute to human disease. Previous works have shown that the extent of RNA editing is sensitive to environmental factors such as interferon presence and hypoxia, and, in an era where worries about our changing environment are ever increasing, understanding how environmentally sensitive mechanisms like RNA editing affect our cells is essential.8,12,14,15 Future research will apply our analysis to the transcriptomes and proteomes of specific disease conditions in order to further clarify the functional and predictive role of APOBEC-mediated C>U RNA editing in human disease.

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