ACTIVATION OF INTERFERON-INDUCIBLE 2'-5'-OLIGOADENYLATE SYNTHETASE BYADENOVIRAL VAI RNA

2'-5' oligoadenylate (2-5(A)) synthetase and protein kinase, RNA activ ated (PKR) are the only two known enzymes that bind double-stranded RN A (dsRNA) and get activated by it. We have previously identified their dsRNA binding domains, which do not have any sequence homology. Here, we report a profound difference between the two enzymes with respect to the structural features of the dsRNA that are required for their ac tivation. The adenoviral virus-associated type I (VAI) RNA cannot acti vate PKR, although it binds to the protein and thereby prevents its ac tivation by authentic dsRNA. In contrast, we observed that VAI RNA can both bind and activate 2-5(A) synthetase. Mutations in VAI RNA, which removed occasional mismatches present in its double-stranded stems, m arkedly enhanced its 2-5(A) synthetase-activating capacity. These muta nts, however, are incapable of activating PKR. Other mutations, which disrupted the structure of the central stem-loop region of the VAI RNA , reduced its ability to activate 2-5(A) synthetase. These debilitated mutants could bind to the synthetase protein, although they fail to b ind to PKR.