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The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme
Abstract
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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“While most APOBECs use single-stranded DNA (ssDNA) as substrate for C-deamination (reviewed in Ref.19), three APOBECs, APOBEC1 (A1)23,24, APOBEC3A (A3A)25, and APOBEC3G (A3G)26, are also shown to deaminate certain cellular single-stranded RNA (ssRNA) targets to cause C-to-U editing.”
From The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness (2022) · cites this paper as [26]
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Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
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Cited by
Sorted by citations
The roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness
Kim, K., Calabrese, P., Wang, S., Qin, C., Rao, Y., Feng, P., & Chen, X. S. (2022) · Scientific Reports · doi:10.1038/s41598-022-19067-x · Cited by 115
Kluesner, M. G., Tasakis, R. N., Lerner, T., Arnold, A., Wüst, S., Binder, M., Webber, B. R., Moriarity, B. S., & Pecori, R. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.07.008 · Cited by 36
Metadata
- Authors
- Sharma, S., Patnaik, S. K., Taggart, R. T., & Baysal, B. E.
- Venue
- Scientific Reports
- Published
- 2016-12-15
- Volume
- 6
- Issue
- 1
- ISSN
- 2045-2322
- PMC
- PMC5156925
- Cited by
- 97
- References
- 3
- Language
- en
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