title: SFP1-mediated prion-dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1.
abstract: [PSI+] is the prion form of the translation termination factor Sup35 (eRF3); [PSI+] strains display nonsense suppression. Another prion-like element, [ISP+], is linked to antisuppression in a specific background. Transcriptional regulator Sfp1 was shown to be responsible for [ISP+] propagation. In this work, we identified SFP1 as a multicopy inducer of [PSI+]-dependent lethality. Sfp1 is likely to up-regulate transcription of genes encoding release factors; however, its overproduction increases Sup35, but not Sup45 protein level. Using the synthetic lethality test, we compared the effects of SFP1 and SUP35 over-expression on the viability of [PSI+] strains. Together with an observation that Sfp1 overproduction leads to an increased accumulation of Sup35 in [PSI+] aggregates, we suggest that excess Sfp1 causes [PSI+] toxicity. Even though SUP45 over-expression is known to compensate for the [PSI+]-dependent lethality, it fails to do so when the lethality is caused by SFP1 over-expression. We discovered that the increased levels of Hsp40 chaperone Sis1 alleviate prion toxicity caused by either SFP1 or SUP35 over-expression and revert back to normal distribution of Sup35 between monomers and aggregate fractions. Finally, we showed that Sfp1 partially colocalizes with Sup35 aggregates, which may contribute to another mechanism of Sfp1-derived [PSI+] prion toxicity.
authors.affiliation: St Petersburg Branch, Vavilov Institute of General Genetics of the Russian Academy of Sciences, St Petersburg, Russia.|Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.|Laboratory of Amyloid Biology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Matveenko
authors.affiliation: Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.|Laboratory of Amyloid Biology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Polina B
authors.initials: PB
authors.lastname: Drozdova
authors.affiliation: Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Belousov
authors.affiliation: St Petersburg Branch, Vavilov Institute of General Genetics of the Russian Academy of Sciences, St Petersburg, Russia.|Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Svetlana E
authors.initials: SE
authors.lastname: Moskalenko
authors.affiliation: Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.|Laboratory of Amyloid Biology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Stanislav A
authors.initials: SA
authors.lastname: Bondarev
authors.affiliation: Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Yury A
authors.initials: YA
authors.lastname: Barbitoff
authors.affiliation: St Petersburg Branch, Vavilov Institute of General Genetics of the Russian Academy of Sciences, St Petersburg, Russia.|Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.|All-Russia Research Institute for Agricultural Microbiology, Pushkin, St Petersburg, Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Nizhnikov
authors.affiliation: Department of Genetics and Biotechnology, Saint Petersburg State University, St Petersburg, Russia.|Laboratory of Amyloid Biology, Saint Petersburg State University, St Petersburg, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Zhouravleva
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D005800:Genes, Fungal; D005804:Genes, Lethal; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D009154:Mutation; D010454:Peptide Termination Factors / Q000378:metabolism*; D000072002:Prion Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D050956:HSP40 Heat-Shock Proteins; D010454:Peptide Termination Factors; D000072002:Prion Proteins; C117421:SFP1 protein, S cerevisiae; C070320:SIS1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins