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The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme

APOBEC3G is a cytidine deaminase with two homologous domains and restricts retroelements and HIV-1. APOBEC3G deaminates single-stranded DNAs via its C-terminal domain, whereas the N-terminal domain is considered non-catalytic. Although APOBEC3G is known to bind RNAs, APOBEC3G-mediated RNA editing ha...

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Autores principales: Sharma, Shraddha, Patnaik, Santosh K., Taggart, Robert T., Baysal, Bora E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156925/
https://www.ncbi.nlm.nih.gov/pubmed/27974822
http://dx.doi.org/10.1038/srep39100
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author Sharma, Shraddha
Patnaik, Santosh K.
Taggart, Robert T.
Baysal, Bora E.
author_facet Sharma, Shraddha
Patnaik, Santosh K.
Taggart, Robert T.
Baysal, Bora E.
author_sort Sharma, Shraddha
collection PubMed
description APOBEC3G is a cytidine deaminase with two homologous domains and restricts retroelements and HIV-1. APOBEC3G deaminates single-stranded DNAs via its C-terminal domain, whereas the N-terminal domain is considered non-catalytic. Although APOBEC3G is known to bind RNAs, APOBEC3G-mediated RNA editing has not been observed. We recently discovered RNA editing by the single-domain enzyme APOBEC3A in innate immune cells. To determine if APOBEC3G is capable of RNA editing, we transiently expressed APOBEC3G in the HEK293T cell line and performed transcriptome-wide RNA sequencing. We show that APOBEC3G causes site-specific C-to-U editing of mRNAs from over 600 genes. The edited cytidines are often flanked by inverted repeats, but are largely distinct from those deaminated by APOBEC3A. We verified protein-recoding RNA editing of selected genes including several that are known to be involved in HIV-1 infectivity. APOBEC3G co-purifies with highly edited mRNA substrates. We find that conserved catalytic residues in both cytidine deaminase domains are required for RNA editing. Our findings demonstrate the novel RNA editing function of APOBEC3G and suggest a role for the N-terminal domain in RNA editing.
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spelling pubmed-51569252016-12-20 The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme Sharma, Shraddha Patnaik, Santosh K. Taggart, Robert T. Baysal, Bora E. Sci Rep Article APOBEC3G is a cytidine deaminase with two homologous domains and restricts retroelements and HIV-1. APOBEC3G deaminates single-stranded DNAs via its C-terminal domain, whereas the N-terminal domain is considered non-catalytic. Although APOBEC3G is known to bind RNAs, APOBEC3G-mediated RNA editing has not been observed. We recently discovered RNA editing by the single-domain enzyme APOBEC3A in innate immune cells. To determine if APOBEC3G is capable of RNA editing, we transiently expressed APOBEC3G in the HEK293T cell line and performed transcriptome-wide RNA sequencing. We show that APOBEC3G causes site-specific C-to-U editing of mRNAs from over 600 genes. The edited cytidines are often flanked by inverted repeats, but are largely distinct from those deaminated by APOBEC3A. We verified protein-recoding RNA editing of selected genes including several that are known to be involved in HIV-1 infectivity. APOBEC3G co-purifies with highly edited mRNA substrates. We find that conserved catalytic residues in both cytidine deaminase domains are required for RNA editing. Our findings demonstrate the novel RNA editing function of APOBEC3G and suggest a role for the N-terminal domain in RNA editing. Nature Publishing Group 2016-12-15 /pmc/articles/PMC5156925/ /pubmed/27974822 http://dx.doi.org/10.1038/srep39100 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sharma, Shraddha
Patnaik, Santosh K.
Taggart, Robert T.
Baysal, Bora E.
The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title_full The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title_fullStr The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title_full_unstemmed The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title_short The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
title_sort double-domain cytidine deaminase apobec3g is a cellular site-specific rna editing enzyme
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156925/
https://www.ncbi.nlm.nih.gov/pubmed/27974822
http://dx.doi.org/10.1038/srep39100
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