Factors Affecting Substrate Selection

ADAR activity was first identified due to its ability to extensively modify adenosines in dsRNA. Indeed, the deamination of up to 50% of adenosines in dsRNA destabilized base pairing to such an extent that the activity was initially described as an 'RNA unwindase' (Bass and Weintraub 1987, 1988; Wagner et al. 1989). In such dsRNAs, the likelihood of editing at individual adenosines is determined largely by: (1) the identity of the 5' nucleotide neighbor—G is strongly disfavored; and (2) the distance from the 3'end of the RNA—adenosines less than 20 nt from the 3'end are not deaminated (Polson and Bass 1994). Despite the role of its activity on dsRNAs in the initial characterization of ADAR, it is not yet clear to what extent editing on dsRNAs is an important cellular function. However, it is clear that ADARs edit several RNAs with high specificity and that some of these editing events are highly important (Bass 2002; Gott and Emeson 2000; Seeburg 1998, 2002).

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