1. Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo
- Author
-
Denise Guetard, Marc Sitbon, Jean-Pierre Vartanian, Anne Keriel, Myrtille Renard, Simon Wain-Hobson, Vincent Petit, Rétrovirologie Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
- Subjects
Hypoxanthine Phosphoribosyltransferase ,MESH : Molecular Sequence Data ,MESH : RNA, Messenger ,MESH : DNA, Complementary ,MESH : NIH 3T3 Cells ,viruses ,Muscle Proteins ,MESH: Base Sequence ,Nucleic Acid Denaturation ,MESH : Retroviridae Infections ,MESH: Animals, Newborn ,Mice ,chemistry.chemical_compound ,MESH : Hypoxanthine Phosphoribosyltransferase ,Structural Biology ,Murine leukemia virus ,MESH : RNA ,MESH: Animals ,APOBEC Deaminases ,MESH : Cytidine Deaminase ,Gammaretrovirus ,MESH : Muscle Proteins ,0303 health sciences ,biology ,Nucleotides ,MESH : Animals, Newborn ,030302 biochemistry & molecular biology ,MESH: Leukemia Virus, Murine ,Cytidine ,Cytidine deaminase ,MESH: Apolipoproteins B ,3. Good health ,Leukemia Virus, Murine ,MESH: Retroviridae Infections ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH : Mutation ,MESH: Genome, Viral ,MESH : Genome, Viral ,MESH : Leukemia Virus, Murine ,MESH : Nucleic Acid Denaturation ,APOBEC ,DNA, Complementary ,MESH: Mutation ,APOBEC-1 Deaminase ,Molecular Sequence Data ,MESH: Leukemia, Experimental ,Genome, Viral ,MESH: Nucleic Acid Denaturation ,[ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Muscle Proteins ,03 medical and health sciences ,MESH: RNA ,Cytidine Deaminase ,MESH : Mice ,MESH : RNA Editing ,Animals ,Humans ,MESH: RNA Editing ,RNA, Messenger ,MESH: Mice ,Molecular Biology ,Apolipoproteins B ,MESH: RNA, Messenger ,MESH: Cytidine Deaminase ,030304 developmental biology ,Messenger RNA ,Leukemia, Experimental ,MESH: Molecular Sequence Data ,MESH: Humans ,Base Sequence ,APOBEC1 ,MESH : Humans ,MESH: Tumor Virus Infections ,RNA ,MESH : Apolipoproteins B ,MESH: DNA, Complementary ,biology.organism_classification ,MESH: Hypoxanthine Phosphoribosyltransferase ,Molecular biology ,MESH: Nucleotides ,Tumor Virus Infections ,Animals, Newborn ,chemistry ,Mutation ,NIH 3T3 Cells ,MESH : Nucleotides ,MESH : Leukemia, Experimental ,MESH : Base Sequence ,MESH : Animals ,RNA Editing ,MESH : Tumor Virus Infections ,Retroviridae Infections ,MESH: NIH 3T3 Cells - Abstract
International audience; 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.
- Published
- 2009