Anant S, Mukhopadhyay D, Sankaranand V, Kennedy S, Henderson J O, Davidson N O
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Physiol Cell Physiol. 2001 Dec;281(6):C1904-16. doi: 10.1152/ajpcell.2001.281.6.C1904.
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.
哺乳动物载脂蛋白B（apoB）的C到U RNA编辑由一种多组分全酶催化，该全酶含有单个催化亚基载脂蛋白B mRNA编辑酶1（apobec-1）。我们鉴定了位于6号染色体p21.1上的apobec-1同源物ARCD-1，并确定了其在apoB mRNA编辑中的作用。ARCD-1 mRNA在全身广泛表达；系统发育分析表明它是RNA编辑家族的一个远亲成员。重组ARCD-1表现出胞苷脱氨酶和apoB RNA结合活性，但在体外或体内均不催化C到U的RNA编辑。尽管ARCD-1本身无能力介导apoB mRNA的脱氨基作用，但它能抑制apobec-1介导的C到U RNA编辑。ARCD-1与apobec-1和apobec-1互补因子（ACF）相互作用并形成异源二聚体，定位于转染细胞的细胞核和细胞质中。总之，这些数据表明ARCD-1是一种新型胞苷脱氨酶，它与apobec-1和ACF相互作用以抑制apoB mRNA编辑，可能是通过与apoB RNA编辑全酶的其他蛋白质成分相互作用来实现的。
