title: Ty1 retrotransposition and programmed +1 ribosomal frameshifting require the integrity of the protein synthetic translocation step.
abstract: Programmed ribosomal frameshifting is utilized by a number of RNA viruses to ensure the correct ratio of viral structural to enzymatic proteins for viral particle assembly. Altering frameshifting efficiencies upsets this ratio, inhibiting virus propagation. Two yeast viruses that induce host cell ribosomes to shift translational reading frame were used as tools to explore the interactions between viruses and host cellular protein synthetic machinery. Previous studies showed that the ribosome-inactivating protein pokeweed antiviral protein specifically inhibited propagation of the Ty1 retrotransposable element of yeast as a consequence of inhibition of programmed +1 ribosomal frameshifting. Here, complementary genetic and pharmacological approaches 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 variety of mutant alleles of two host-encoded proteins that are involved in translocation, eukaryotic elongation factor-2 and the ribosome-associated protein 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.
authors.affiliation: Department of Molecular Genetics and Microbiology, Graduate Program in Molecular Biosciences at UMDNJ/Rutgers Universities, The Cancer Institute of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Harger
authors.forename: A
authors.initials: A
authors.lastname: Meskauskas
authors.forename: J
authors.initials: J
authors.lastname: Nielsen
authors.forename: M C
authors.initials: MC
authors.lastname: Justice
authors.forename: J D
authors.initials: JD
authors.lastname: Dinman
mesh_terms: D018965:Frameshifting, Ribosomal; D021381:Protein Transport; D012328:RNA Viruses / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000821:virology*; D019065:Virus Assembly / Q000235:genetics*
chemical_list: D018626:Retroelements