Murine APOBEC1 is a powerful mutator of retroviral and cellular RNA in vitro and in vivo.
Mammalian APOBEC molecules comprise a large family of cytidine deaminases with specificity for RNA and single-stranded DNA (ssDNA). APOBEC1s are invariably highly specific and edit a single residue in a cellular mRNA, while the cellular targets for APOBEC3s are not clearly established, although they may curtail the transposition of some retrotransposons. Two of the seven member human APOBEC3 enzymes strongly restrict human immunodeficiency virus type 1 in vitro and in vivo. We show here that ssDNA hyperediting of an infectious exogenous gammaretrovirus, the Friend-murine leukemia virus, by murine APOBEC1 and APOBEC3 deaminases occurs in vitro. Murine APOBEC1 was able to hyperdeaminate cytidine residues in murine leukemia virus genomic RNA as well. Analysis of the edited sites shows that the deamination in vivo was due to mouse APOBEC1 rather than APOBEC3. Furthermore, murine APOBEC1 is able to hyperedit its primary substrate in vivo, the apolipoprotein B mRNA, and a variety of heterologous RNAs. In short, murine APOBEC1 is a hypermutator of both RNA and ssDNA in vivo, which could exert occasional side effects upon overexpression.
Petit
Vincent
V
Unité de Rétrovirologie Moléculaire, CNRS URA, Institut Pasteur, Paris, France.
Guétard
Denise
D
Renard
Myrtille
M
Keriel
Anne
A
Sitbon
Marc
M
Wain-Hobson
Simon
S
Vartanian
Jean-Pierre
JP
D000071478:APOBEC Deaminases; D000071479:APOBEC-1 Deaminase; D000818:Animals; D000831:Animals, Newborn; D001055:Apolipoproteins B / Q000235:genetics; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000201:enzymology / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D041681:NIH 3T3 Cells; D009691:Nucleic Acid Denaturation; D009711:Nucleotides; D012313:RNA / Q000235:genetics*; D017393:RNA Editing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012192:Retroviridae Infections / Q000201:enzymology; D014412:Tumor Virus Infections / Q000201:enzymology / Q000235:genetics
D001055:Apolipoproteins B; D018076:DNA, Complementary; D009124:Muscle Proteins; D009711:Nucleotides; D012333:RNA, Messenger; D012313:RNA; D007041:Hypoxanthine Phosphoribosyltransferase; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D000071478:APOBEC Deaminases; C485629:Apobec2 protein, mouse; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase