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Identification of new genes that affect [PSI +] prion toxicity in Saccharomyces cerevisiae yeast

Abstract

Translation termination is an important step in gene expression. Its correct processing is governed by eRF1 (Sup45) and eRF3 (Sup35) proteins. In Saccharomyces cerevisiae, mutations in the corresponding genes, as well as Sup35 aggregation in [PSI +] cells that propagate the prion form of Sup35 lead to inaccurate stop codon recognition and, consequently, nonsense suppression. The presence of stronger prion variants results in the more efficient suppression of nonsense mutations. Previously, we proposed a synthetic lethality test that enables the identification of genes that may influence either translation termination factors or [PSI +] manifestation. This is based on the fact that the combination of sup45 mutations with the strong [PSI +] prion variant in diploids is lethal. In this work, a set of genes that were previously shown to enhance nonsense suppression was analyzed. It was found that ABF1, FKH2, and REB1 overexpression decreased the growth of strains in a prion-dependent manner and, thus, might influence [PSI +] prion toxicity. It was also shown that the synthetic lethality of [PSI +] and sup45 mutations increased with the overexpression of GLN3 and MOT3 that encode Q/N-rich transcription factors. An analysis of the effects of their expression on the transcription of the release factors genes revealed an increase in SUP35 transcription in both cases. Since SUP35 overexpression is known to be toxic in [PSI +] strains, these genes apparently enhance [PSI +] toxicity via the regulation of SUP35 transcription.

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Correspondence to G. A. Zhouravleva.

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Original Russian Text © A.G. Matveenko, M.V. Belousov, S.A. Bondarev, S.E. Moskalenko, G.A. Zhouravleva, 2016, published in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 5, pp. 803–813.

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Matveenko, A.G., Belousov, M.V., Bondarev, S.A. et al. Identification of new genes that affect [PSI +] prion toxicity in Saccharomyces cerevisiae yeast. Mol Biol 50, 710–718 (2016). https://doi.org/10.1134/S0026893316050113

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Keywords

  • prion
  • [PSI +]
  • translation termination
  • eRF1
  • eRF3
  • SUP45
  • SUP35
  • Saccharomyces cerevisiae