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The Role of C-to-U RNA Editing in Human Biodiversity

Intra-organism biodiversity is thought to arise from epigenetic modification of our constituent genes and post-translational modifications after mRNA is translated into proteins. We have found that post-transcriptional modification, also known as RNA editing, is also responsible for a significant am...

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Autores principales: Van Norden, Melissa, Falls, Zackary, Mandloi, Sapan, Segal, Brahm, Baysal, Bora, Samudrala, Ram, Elkin, Peter L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418052/
https://www.ncbi.nlm.nih.gov/pubmed/37577456
http://dx.doi.org/10.1101/2023.07.31.550344
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author Van Norden, Melissa
Falls, Zackary
Mandloi, Sapan
Segal, Brahm
Baysal, Bora
Samudrala, Ram
Elkin, Peter L.
author_facet Van Norden, Melissa
Falls, Zackary
Mandloi, Sapan
Segal, Brahm
Baysal, Bora
Samudrala, Ram
Elkin, Peter L.
author_sort Van Norden, Melissa
collection PubMed
description Intra-organism biodiversity is thought to arise from epigenetic modification of our constituent genes and post-translational modifications after mRNA is translated into proteins. We have found that post-transcriptional modification, also known as RNA editing, is also responsible for a significant amount of our biodiversity, substantively expanding this story. The APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family RNA editing enzymes APOBEC3A and APOBEC3G catalyze the deamination of cytosines to uracils (C>U) in specific stem-loop structures.(1,2) We used RNAsee (RNA site editing evaluation), a tool developed to predict the locations of APOBEC3A/G RNA editing sites, to determine whether known single nucleotide polymorphisms (SNPs) in DNA could be replicated in RNA via RNA editing. About 4.5% of non-synonymous SNPs which result in C>U changes in RNA, and about 5.4% of such SNPs labelled as pathogenic, were identified as probable sites for APOBEC3A/G editing. This suggests that the variant proteins created by these DNA mutations may also be created by transient RNA editing, with the potential to affect human health. Those SNPs identified as potential APOBEC3A/G-mediated RNA editing sites were disproportionately associated with cardiovascular diseases, digestive system diseases, and musculoskeletal diseases. Future work should focus on common sites of RNA editing, any variant proteins created by these RNA editing sites, and the effects of these variants on protein diversity and human health. 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, often stimulated by environmental factors, could account for a significant degree of the protein biodiversity leading to human disease. In an era where worries about our changing environment are ever increasing, from the warming of our climate to the emergence of new diseases to the infiltration of microplastics and pollutants into our bodies, understanding how environmentally sensitive mechanisms like RNA editing affect our own cells is essential.
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spelling pubmed-104180522023-08-12 The Role of C-to-U RNA Editing in Human Biodiversity Van Norden, Melissa Falls, Zackary Mandloi, Sapan Segal, Brahm Baysal, Bora Samudrala, Ram Elkin, Peter L. bioRxiv Article Intra-organism biodiversity is thought to arise from epigenetic modification of our constituent genes and post-translational modifications after mRNA is translated into proteins. We have found that post-transcriptional modification, also known as RNA editing, is also responsible for a significant amount of our biodiversity, substantively expanding this story. The APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family RNA editing enzymes APOBEC3A and APOBEC3G catalyze the deamination of cytosines to uracils (C>U) in specific stem-loop structures.(1,2) We used RNAsee (RNA site editing evaluation), a tool developed to predict the locations of APOBEC3A/G RNA editing sites, to determine whether known single nucleotide polymorphisms (SNPs) in DNA could be replicated in RNA via RNA editing. About 4.5% of non-synonymous SNPs which result in C>U changes in RNA, and about 5.4% of such SNPs labelled as pathogenic, were identified as probable sites for APOBEC3A/G editing. This suggests that the variant proteins created by these DNA mutations may also be created by transient RNA editing, with the potential to affect human health. Those SNPs identified as potential APOBEC3A/G-mediated RNA editing sites were disproportionately associated with cardiovascular diseases, digestive system diseases, and musculoskeletal diseases. Future work should focus on common sites of RNA editing, any variant proteins created by these RNA editing sites, and the effects of these variants on protein diversity and human health. 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, often stimulated by environmental factors, could account for a significant degree of the protein biodiversity leading to human disease. In an era where worries about our changing environment are ever increasing, from the warming of our climate to the emergence of new diseases to the infiltration of microplastics and pollutants into our bodies, understanding how environmentally sensitive mechanisms like RNA editing affect our own cells is essential. Cold Spring Harbor Laboratory 2023-07-31 /pmc/articles/PMC10418052/ /pubmed/37577456 http://dx.doi.org/10.1101/2023.07.31.550344 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Van Norden, Melissa
Falls, Zackary
Mandloi, Sapan
Segal, Brahm
Baysal, Bora
Samudrala, Ram
Elkin, Peter L.
The Role of C-to-U RNA Editing in Human Biodiversity
title The Role of C-to-U RNA Editing in Human Biodiversity
title_full The Role of C-to-U RNA Editing in Human Biodiversity
title_fullStr The Role of C-to-U RNA Editing in Human Biodiversity
title_full_unstemmed The Role of C-to-U RNA Editing in Human Biodiversity
title_short The Role of C-to-U RNA Editing in Human Biodiversity
title_sort role of c-to-u rna editing in human biodiversity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418052/
https://www.ncbi.nlm.nih.gov/pubmed/37577456
http://dx.doi.org/10.1101/2023.07.31.550344
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