A mechanism for the control of protein synthesis by adenovirus VA RNA I

Abstract

In the absence of VA RNA I, protein synthesis in adenovirus-infected HeLa cells fails because of defective initiation. Earlier work showed that the defect results from phosphorylation of the initiation factor elF-2 on its α subunit. We have identified the protein kinase responsible as the dsRNA-activated inhibitor of protein synthesis (DAI). DAI is present in uninfected HeLa cells at a basal level and in a largely inactive state. It is activated in cells infected with the adenovirus mutant Ad5 dl331, which produces no VA RNA I, but not in cells infected with wild-type virus. Activation occurs during the late phase of infection with the mutant virus, and the activator appears to be dsRNA produced by symmetrical transcription of the viral genome. VA RNA I antagonizes the activation of DAI by dsRNA, but it cannot inhibit the activity of DAI once activated. We propose a mechanism for VA RNA I action based on its partially double-stranded nature.