title: Highly diverged homologs of Saccharomyces cerevisiae mitochondrial mRNA-specific translational activators have orthologous functions in other budding yeasts.
abstract: Translation of mitochondrially coded mRNAs in Saccharomyces cerevisiae depends on membrane-bound mRNA-specific activator proteins, whose targets lie in the mRNA 5'-untranslated leaders (5'-UTLs). In at least some cases, the activators function to localize translation of hydrophobic proteins on the inner membrane and are rate limiting for gene expression. We searched unsuccessfully in divergent budding yeasts for orthologs of the COX2- and COX3-specific translational activator genes, PET111, PET54, PET122, and PET494, by direct complementation. However, by screening for complementation of mutations in genes adjacent to the PET genes in S. cerevisiae, we obtained chromosomal segments containing highly diverged homologs of PET111 and PET122 from Saccharomyces kluyveri and of PET111 from Kluyveromyces lactis. All three of these genes failed to function in S. cerevisiae. We also found that the 5'-UTLs of the COX2 and COX3 mRNAs of S. kluyveri and K. lactis have little similarity to each other or to those of S. cerevisiae. To determine whether the PET111 and PET122 homologs carry out orthologous functions, we deleted them from the S. kluyveri genome and deleted PET111 from the K. lactis genome. The pet111 mutations in both species prevented COX2 translation, and the S. kluyveri pet122 mutation prevented COX3 translation. Thus, while the sequences of these translational activator proteins and their 5'-UTL targets are highly diverged, their mRNA-specific functions are orthologous.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853-2703, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Costanzo
authors.forename: N
authors.initials: N
authors.lastname: Bonnefoy
authors.forename: E H
authors.initials: EH
authors.lastname: Williams
authors.forename: G D
authors.initials: GD
authors.lastname: Clark-Walker
authors.forename: T D
authors.initials: TD
authors.lastname: Fox
mesh_terms: D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D000818:Animals; D051546:Cyclooxygenase 2; D003576:Electron Transport Complex IV / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D007527:Isoenzymes / Q000235:genetics*; D007716:Kluyveromyces / Q000145:classification / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010448:Peptide Initiation Factors; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D014176:Protein Biosynthesis; D012313:RNA; D012331:RNA, Fungal; D000077278:RNA, Mitochondrial; D012440:Saccharomyces / Q000145:classification / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020121:5' Untranslated Regions; D005656:Fungal Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C087048:PET111 protein, S cerevisiae; D010448:Peptide Initiation Factors; D012331:RNA, Fungal; D000077278:RNA, Mitochondrial; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C093750:COX3 protein, S cerevisiae; D003576:Electron Transport Complex IV