Articles producció científica> Bioquímica i Biotecnologia

The yeast mRNA-binding protein Cth2 post-transcriptionally modulates ergosterol biosynthesis in response to iron deficiency

  • Identification data

    Identifier: imarina:9325567
    Authors:
    Jordá TRozès NMartínez-Pastor MTPuig S
    Abstract:
    Sterol synthesis is an iron-dependent metabolic pathway in eukaryotes. Consequently, fungal ergosterol biosynthesis (ERG) is down-regulated in response to iron deficiency. In this report, we show that, upon iron limitation or overexpression of the iron-regulated mRNA-binding protein Cth2, the yeast Saccharomyces cerevisiae down-regulates the three initial enzymatic steps of ergosterol synthesis (ERG1, ERG7 and ERG11). Mechanistically, we show that Cth2 protein limits the translation and promotes the decrease in the mRNA levels of these specific ERG genes, which contain consensus Cth2-binding sites defined as AU-rich elements (AREs). Thus, expression of CTH2 leads to the accumulation of initial sterol intermediates, such as squalene, and to the drop of ergosterol levels. Changes in CTH2 expression levels disturb the response of yeast cells to stresses related to membrane integrity such as high ethanol and sorbitol concentrations. Therefore, CTH2 should be considered as a critical regulatory factor of ergosterol biosynthesis during iron deficiency.Copyright © 2023. Published by Elsevier B.V.
  • Others:

    Author, as appears in the article.: Jordá T; Rozès N; Martínez-Pastor MT; Puig S
    Department: Bioquímica i Biotecnologia
    URV's Author/s: Rozès, Nicolas Andre Louis
    Keywords: Yeast Ethanol Ergosterol Erg Cth2 kinase ergosterol erg decay cth2
    Abstract: Sterol synthesis is an iron-dependent metabolic pathway in eukaryotes. Consequently, fungal ergosterol biosynthesis (ERG) is down-regulated in response to iron deficiency. In this report, we show that, upon iron limitation or overexpression of the iron-regulated mRNA-binding protein Cth2, the yeast Saccharomyces cerevisiae down-regulates the three initial enzymatic steps of ergosterol synthesis (ERG1, ERG7 and ERG11). Mechanistically, we show that Cth2 protein limits the translation and promotes the decrease in the mRNA levels of these specific ERG genes, which contain consensus Cth2-binding sites defined as AU-rich elements (AREs). Thus, expression of CTH2 leads to the accumulation of initial sterol intermediates, such as squalene, and to the drop of ergosterol levels. Changes in CTH2 expression levels disturb the response of yeast cells to stresses related to membrane integrity such as high ethanol and sorbitol concentrations. Therefore, CTH2 should be considered as a critical regulatory factor of ergosterol biosynthesis during iron deficiency.Copyright © 2023. Published by Elsevier B.V.
    Thematic Areas: Structural biology Molecular biology Medicina i Genetics Farmacia Ciências biológicas ii Ciências biológicas i Biotecnología Biophysics Biochemistry & molecular biology Biochemistry
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: nicolasrozes@urv.cat
    Author identifier: 0000-0001-9718-3429
    Record's date: 2024-08-03
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.sciencedirect.com/science/article/pii/S1874939923000548
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms. 1866 (3): 194959-194959
    APA: Jordá T; Rozès N; Martínez-Pastor MT; Puig S (2023). The yeast mRNA-binding protein Cth2 post-transcriptionally modulates ergosterol biosynthesis in response to iron deficiency. Biochimica Et Biophysica Acta-Gene Regulatory Mechanisms, 1866(3), 194959-194959. DOI: 10.1016/j.bbagrm.2023.194959
    Article's DOI: 10.1016/j.bbagrm.2023.194959
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2023
    Publication Type: Journal Publications
  • Keywords:

    Biochemistry,Biochemistry & Molecular Biology,Biophysics,Genetics,Molecular Biology,Structural Biology
    Yeast
    Ethanol
    Ergosterol
    Erg
    Cth2
    kinase
    ergosterol
    erg
    decay
    cth2
    Structural biology
    Molecular biology
    Medicina i
    Genetics
    Farmacia
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Biophysics
    Biochemistry & molecular biology
    Biochemistry
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