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APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages

Sharma, Shraddha, Patnaik, Santosh K., Thomas Taggart, R., Kannisto, Eric D., Enriquez, Sally M., Gollnick, Paul, Baysal, Bora E.·2015·Nature Communications

Abstract

The extent, regulation and enzymatic basis of RNA editing by cytidine deamination are incompletely understood. Here we show that transcripts of hundreds of genes undergo site-specific C>U RNA editing in macrophages during M1 polarization and in monocytes in response to hypoxia and interferons. This editing alters the amino acid sequences for scores of proteins, including many that are involved in pathogenesis of viral diseases. APOBEC3A, which is known to deaminate cytidines of single-stranded DNA and to inhibit viruses and retrotransposons, mediates this RNA editing. Amino acid residues of APOBEC3A that are known to be required for its DNA deamination and anti-retrotransposition activities were also found to affect its RNA deamination activity. Our study demonstrates the cellular RNA editing activity of a member of the APOBEC3 family of innate restriction factors and expands the understanding of C>U RNA editing in mammals.

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  • A3A showed a preferred dinucleotide UC motif for editing.

    “A3A showed a preferred dinucleotide UC motif, consistent with previous reports about the preferred motif for A3A-mediated editing of cellular RNA targets25,54.”
  • Three APOBECs, APOBEC1 (A1), APOBEC3A (A3A), and APOBEC3G (A3G), are shown to deaminate certain cellular single-stranded RNA targets to cause C-to-U editing.

    “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.”
  • A3A prefers for an UCa/u trinucleotide motif and A1 + A1CF prefers ACu/a motif.

    “Analysis of the sequence contexts around the significant target C sites (with ± 5 nucleotides from target C) showed that A3A prefers for an UCa/u trinucleotide motif and A1 + A1CF prefers ACu/a motif (Fig. 2A), which is consistent with the reported motif preference for RNA editing by A3A and A125,31.”
  • Some cellular RNA targets with stem-loop structures are favored by A3A and A1 editing.

    “Prior reports show that some cellular RNA targets with stem-loop structures are favored by A3A and A1 editing25,28,34,54.”

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Metadata

Authors
Sharma, S., Patnaik, S. K., Thomas Taggart, R., Kannisto, E. D., Enriquez, S. M., Gollnick, P., & Baysal, B. E.
Venue
Nature Communications
Published
2015-04-21
Volume
6
Issue
1
ISSN
2041-1723
Cited by
264
References
7
Language
en

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