Two Molecular Weight Forms of Human 2′,5′-Oligoadenylate Synthetase Have Different Activation Requirements

Ion-exchange and gel filtration chromatography were used to purify partially a 33,000-dalton (33 kD) 2′,5′-oligoadenylate synthetase and a 110,000-dalton (110 kD) 2′,5′-oligoadenylate synthetase from HeLa cells treated with α-interferon (IFN-α). The 33-kD enzyme was optimally activated only when double-stranded RNA was added in 100 to 1000-fold excess of the concentration activating the 110-kD enzyme. Certain double- or triple-stranded RNAs, which were observed to activate the 110-kD enzyme, failed to activate the 33-kD enzyme, even when added at high concentration. The 110-kD enzyme manifested an alkaline pH optimum of 7.5 or more and the 33-kD enzyme an acidic pH optimum of 6.0 or less. The results suggest that intracellular activation of the two forms of 2′,5′-oligoadenylate synthetase may occur under markedly different conditions.