title: Translational misreading: mutations in translation elongation factor 1alpha differentially affect programmed ribosomal frameshifting and drug sensitivity.
abstract: The translation elongation feactor 1alpha (EF-1alpha) catalyzes the critical step of delivering aminoacyl-tRNAs to the elongating ribosome. A series of Saccharomyces cerevisiae strains containing mutant alleles of the TEF2 gene encoding EF-1alpha have phenotypes consistent with effects on cellular processes related to translation. These include (1) conditional growth defects, (2) antibiotic sensitivity or resistance, (3) altered +1 or -1 ribosomal frameshifting efficiencies, and (4) altered maintenance of the killer phenotype. Although all the mutant alleles were isolated as dominant +1 frameshift suppressors, the effects of these mutations on the cell are quite different when present as the only form of EF-1alpha. Allele-specific effects are observed with regard to their ability to alter the efficiency of programmed +1 frameshifting as opposed to programmed -1 ribosomal frameshifting. The significantly altered efficiency of -1 frameshifting in strains containing the TEF2-4 and TEF2-9 mutant alleles further correlates with a reduced ability to maintain the killer phenotype and the M1 satellite virus of L-A, an in vivo assay of translational fidelity. In light of the proposed models regarding the different A- and P-site occupancy states required for +1 or -1 ribosomal frameshifting, these results aid analysis of interactions between EF-1alpha and the translational apparatus.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School and The Graduate Programs in Molecular Biosciences, Rutgers University and UMDNJ RWJMS, Piscataway, 08854-5635, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Dinman
authors.forename: T G
authors.initials: TG
authors.lastname: Kinzy
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D016368:Frameshift Mutation; D016153:Genes, Suppressor; D008958:Models, Molecular; D009154:Mutation; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000821:virology; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D004268:DNA-Binding Proteins; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C057183:TEF2 protein, S cerevisiae