APOBEC3 proteins inhibit LINE-1 retrotransposition in the absence of ORF1p binding.
Members of the apolipoprotein B mRNA editing complex polypeptide 1-like (APOBEC) family of enzymes exhibit inhibitory activity against a variety of exogenous and endogenous retroviruses including retrotransposons, such as long interspersed element 1 (LINE-1). Indeed, human APOBEC3A, APOBEC3B, and APOBEC3F inhibit retrotransposition of human LINE-1, mouse IAP and MusD retrotransposons. In our study, we examined whether the inhibitory effect of APOBEC3 proteins correlates with APOBEC3 ability to bind the LINE-1 ORF1 protein. We examined the interactions between the LINE-1 ORF1 protein and the most potent LINE-1 retrotransposon inhibitors, human APOBEC3A and APOBEC3B, by immunofluorescence and immunoprecipitation. Although human APOBEC3A shows the highest inhibitory potency against LINE-1 retrotransposon, no direct interactions were identified either by immunofluorescence or by co-immunoprecipitation. APOBEC3B binds to LINE-1 ORF1 protein, yet no co-localization was detected. We concluded that APOBEC3 proteins interfere indirectly with the LINE-1 retrotransposition pathway, probably through interference with RNA targeting.
Lovsin
Nika
N
Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. nika.lovsin@fkkt.uni-lj.si
Peterlin
B Matija
BM
D000071479:APOBEC-1 Deaminase; D000818:Animals; D001665:Binding Sites; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D051379:Mice; D016366:Open Reading Frames / Q000235:genetics*; D014162:Transfection
D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase