A novel elF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols

M. P. Ashe, J. W. Slaven, S. K. De Long, S. Ibrahimo, A. B. Sachs

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Fusel alcohols are natural products of amino acid catabolism in the yeast Saccharomyces cerevisiae that cause morphological changes similar to those seen during pseudohyphal growth. We have discovered that certain of these alcohols, including butanol and isoamyl alcohol, bring about a rapid inhibition of translation at the initiation step. This inhibition is strain specific and is not explained by previously described translational control pathways. Using genetic mapping, we have identified a proline to serine allelic variation at amino acid 180 of the GCD1 gene product as the genetic locus that allows translational regulation upon butanol addition. Gcdlp forms part of the eIF2B guanine nucleotide complex that is responsible for recycling eIF2-GDP to eIF2-GTP. This represents one of the key limiting steps of translation initiation and we provide evidence that fusel alcohols target eIF2B in order to bring about translational regulation.
    Original languageEnglish
    Pages (from-to)6464-6474
    Number of pages10
    JournalEMBO Journal
    Volume20
    Issue number22
    DOIs
    Publication statusPublished - 15 Nov 2001

    Keywords

    • Eif2
    • Fusel alcohols
    • Gcd1p
    • Translation

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