ARCD-1, an apobec-1-related cytidine deaminase, exerts a dominant negative effect on C to U RNA editing

Abstract

Mammalian apolipoprotein B (apoB) C to U RNA editing is catalyzed by a multicomponent holoenzyme containing a single catalytic subunit, apobec-1. We have characterized an apobec-1 homologue, ARCD-1, located on chromosome 6p21.1, and determined its role in apoB mRNA editing. ARCD-1 mRNA is ubiquitously expressed; phylogenetic analysis reveals it to be a distant member of the RNA editing family. Recombinant ARCD-1 demonstrates cytidine deaminase and apoB RNA binding activity but does not catalyze C to U RNA editing, either in vitro or in vivo. Although not competent itself to mediate deamination of apoB mRNA, ARCD-1 inhibits apobec-1-mediated C to U RNA editing. ARCD-1 interacts and heterodimerizes with both apobec-1 and apobec-1 complementation factor (ACF) and localizes to both the nucleus and cytoplasm of transfected cells. Together, the data suggest that ARCD-1 is a novel cytidine deaminase that interacts with apobec-1 and ACF to inhibit apoB mRNA editing, possibly through interaction with other protein components of the apoB RNA editing holoenzyme.

Zinc-binding Domain-dependent, Deaminase-independent Actions of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide 2 (Apobec2), Mediate Its Effect on Zebrafish Retina Regeneration

“…Previous biochemical studies of mammalian Apobec2 proteins have questioned their catalytic activity (9 -11) and their ability to bind large polynucleotides (3,4). Here we show that Apobec2a,2b, like their mammalian orthologs, do not increase survival in bacterial mutagenesis assays.…”

“…Apobec2 was the second Apobec family member identified (2,3). Although its overexpression has been correlated with tumor formation, and its deletion correlated with perturbations in muscle development, retina regeneration, and left-right axis specification, the biochemical function of Apobec2 remains unknown (4 -8).…”

“…Although its overexpression has been correlated with tumor formation, and its deletion correlated with perturbations in muscle development, retina regeneration, and left-right axis specification, the biochemical function of Apobec2 remains unknown (4 -8). Unlike other Apobecs, Apobec2 fails to induce cytosine deaminase-dependent mutations in bacterial and yeast-based mutagenesis assays (deamination of cytosine results in its conversion to uracil) (9 -11), and the ability of Apobec2 to bind polynucleotides is limited (3,4). Although biochemical data are lacking, prominent models of Apobec2 function include cytosine deaminase-dependent DNA demethylation (12,13) and C-to-U mRNA editing (5,6,8).…”

Analysis of DNA methylation reveals a partial reprogramming of the Müller glia genome during retina regeneration

“…It is possible that these proteins, like other Apobecs, catalytically edit RNAs, but it is also possible that they perform some function that is independent of a deaminase activity. Indeed, some have questioned whether Apobec2 proteins are catalytically active and whether they bind polynucleotides (36)(37)(38)(39). Further work is needed to shed light on the mechanism of these proteins.…”

Biochemical and molecular characterization of two cytidine deaminases in the nematode Caenorhabditis elegans

“…The distance matrix was generated using the PROTDIST program, followed by the generation of a tree by the KITSCH programme, which was plotted using the DRAWTREE program [18].…”