title: A novel eIF2B-dependent mechanism of translational control in yeast as a response to fusel alcohols.
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. Gcd1p 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.
authors.affiliation: Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD, UK. mark.p.ashe@umist.ac.uk
authors.forename: M P
authors.initials: MP
authors.lastname: Ashe
authors.forename: J W
authors.initials: JW
authors.lastname: Slaven
authors.forename: S K
authors.initials: SK
authors.lastname: De Long
authors.forename: S
authors.initials: S
authors.lastname: Ibrahimo
authors.forename: A B
authors.initials: AB
authors.lastname: Sachs
mesh_terms: D000438:Alcohols / Q000378:metabolism*; D000483:Alleles; D000440:Butanols / Q000494:pharmacology; D002874:Chromosome Mapping; D004171:Diploidy; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism*; D019143:Evolution, Molecular; D017930:Genes, Reporter; D014644:Genetic Variation; D006147:Guanine / Q000378:metabolism; D015151:Immunoblotting; D007763:Lac Operon; D008540:Meiosis; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D000439:Pentanols / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011392:Proline / Q000235:genetics; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000438:Alcohols; D000440:Butanols; D020717:Eukaryotic Initiation Factor-2B; D000439:Pentanols; D029701:Saccharomyces cerevisiae Proteins; C007807:fusel oil; D012694:Serine; D013395:Sucrose; D006147:Guanine; D011392:Proline; D008715:Methionine; C029683:isopentyl alcohol; D011494:Protein Kinases; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D001616:beta-Galactosidase