ARCD-1, an apobec-1-related cytidine deaminase, exerts a dominant negative effect on C to U RNA editing.
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.
Anant
S
S
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. sanant@im.wustl.edu
Mukhopadhyay
D
D
Sankaranand
V
V
Kennedy
S
S
Henderson
J O
JO
Davidson
N O
NO
D000071479:APOBEC-1 Deaminase; D000595:Amino Acid Sequence; D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D017393:RNA Editing; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution
D001055:Apolipoproteins B; D011994:Recombinant Proteins; D012313:RNA; C442249:ARCD-1 cytidine deaminase; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase