title: Translational errors as an early event in prion conversion.
abstract: A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.
authors.affiliation: Institut de Génétique et Microbiologie, UMR CNRS C8621, Université Paris-Sud, Orsay, France.
authors.forename: I
authors.initials: I
authors.lastname: Hatin
authors.forename: L
authors.initials: L
authors.lastname: Bidou
authors.forename: C
authors.initials: C
authors.lastname: Cullin
authors.forename: J P
authors.initials: JP
authors.lastname: Rousset
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018965:Frameshifting, Ribosomal / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology; D005979:Glutathione Peroxidase; D006801:Humans; D010641:Phenotype; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C010680:antibiotic G 418; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae