OVEREXPRESSION OF APOBEC-1 RESULTS IN MOORING SEQUENCE-DEPENDENT PROMISCUOUS RNA EDITING

Apolipoprotein B (apoB) RNA editing involves site-specific deamination of a cytidine to a uridine. A mooring sequence, a spacer region, and a regulator region are components of the apoB RNA editing motif of whi ch only the mooring sequence is both necessary and sufficient for edit osome assembly and editing. The catalytic component of the editosome i s APOBEC-1. In rat hepatoma, stable cell lines, overexpression of APOB EC-1 resulted in 3-6-fold stimulation of the editing efficiency on eit her rat endogenous apoB RNA or transiently expressed human apoB RNA, I n these cell lines, cytidines in addition to the one at the wild type site were edited, The occurrence and efficiency of this ''promiscuous' ' editing increased with increasing expression of APOBEC-1, Promiscuou s editing was restricted to cytidines 5' of the mooring sequence and o nly occurred on RNAs that had been edited at the wild type site, Moreo ver, RNAs with mutant editing motifs supported high efficiency but low fidelity editing in the presence of high levels of APOBEC-1. This stu dy demonstrates that overexpression of APOBEC-1 can increase the effic iency of site specific editing but can also result in promiscuous edit ing.