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

Research output

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)710-718
Number of pages9
JournalMolecular Biology
Volume50
Issue number5
DOIs
Publication statusPublished - Sep 2016

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Prions
Saccharomyces cerevisiae
Yeasts
Genes
Mutation
Transcription Factors
Terminator Codon
Nonsense Codon
Poisons
Diploidy
Gene Expression
Growth
Synthetic Lethal Mutations

Scopus subject areas

  • Structural Biology
  • Biophysics

Cite this

@article{479722d62e0f460bac1d879a7ef88eed,
title = "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.",
keywords = "prion, [PSI+], translation termination, eRF1, eRF3, SUP45, SUP35, Saccharomyces cerevisiae, CHAIN RELEASE FACTORS, DE-NOVO APPEARANCE, TRANSLATION TERMINATION, ANTAGONISTIC INTERACTIONS, ENVIRONMENTAL-STRESS, SYNTHETIC LETHALITY, FACTOR ERF3, SUP45 GENE, SUP35 GENE, IN-VIVO",
author = "Matveenko, {A. G.} and Belousov, {M. V.} and Bondarev, {S. A.} and Moskalenko, {S. E.} and Zhouravleva, {G. A.}",
year = "2016",
month = "9",
doi = "10.1134/S0026893316050113",
language = "English",
volume = "50",
pages = "710--718",
journal = "Molecular Biology",
issn = "0026-8933",
publisher = "Pleiades Publishing",
number = "5",

}

TY - JOUR

T1 - Identification of new genes that affect [PSI (+)] prion toxicity in Saccharomyces cerevisiae yeast

AU - Matveenko, A. G.

AU - Belousov, M. V.

AU - Bondarev, S. A.

AU - Moskalenko, S. E.

AU - Zhouravleva, G. A.

PY - 2016/9

Y1 - 2016/9

N2 - 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.

AB - 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.

KW - prion

KW - [PSI+]

KW - translation termination

KW - eRF1

KW - eRF3

KW - SUP45

KW - SUP35

KW - Saccharomyces cerevisiae

KW - CHAIN RELEASE FACTORS

KW - DE-NOVO APPEARANCE

KW - TRANSLATION TERMINATION

KW - ANTAGONISTIC INTERACTIONS

KW - ENVIRONMENTAL-STRESS

KW - SYNTHETIC LETHALITY

KW - FACTOR ERF3

KW - SUP45 GENE

KW - SUP35 GENE

KW - IN-VIVO

UR - http://www.scopus.com/inward/record.url?scp=84991669582&partnerID=8YFLogxK

U2 - 10.1134/S0026893316050113

DO - 10.1134/S0026893316050113

M3 - Article

AN - SCOPUS:84991669582

VL - 50

SP - 710

EP - 718

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 5

ER -