Ty1 retrotransposition and programmed+1 ribosomal frameshifting require the integrity of the protein synthetic translocation step

Programmed ribosomal frameshifting is utilized by a number of RNA viruses t o ensure the correct ratio of viral structural to enzymatic proteins for vi ral particle assembly. Altering frameshifting efficiencies upsets this rati o, inhibiting virus propagation. Two yeast viruses that induce host cell ri bosomes to shift translational reading frame were used as tools to explore the interactions between viruses and host cellular protein synthetic machin ery. Previous studies showed that the ribosome-inactivating protein pokewee d antiviral protein specifically inhibited propagation of the Ty1 retrotran sposable element of yeast as a consequence of inhibition of programmed +1 r ibosomal frameshifting. Here, complementary genetic and pharmacological app roaches were employed to test whether inhibition of Ty1 retrotransposition is a general feature of alterations in the translocation step of elongation and +1 frameshifting. The results demonstrate that cells harboring a varie ty of mutant alleles of two host-encoded proteins that are involved in tran slocation, eukaryotic elongation factor-2 and the ribosome-associated prote in RPP0, have Ty1 propagation defects. We also show that sordarin, a fungus -specific inhibitor of eEF-2 function, specifically inhibits programmed +1 ribosomal frameshifting and Ty1 retrotransposition. These findings serve to link inhibition of Ty1 retrotransposition and +1 frameshifting to changes in the translocation step of elongation. (C) 2001 Academic Press.