title: Translational misreading: a tRNA modification counteracts a +2 ribosomal frameshift.
abstract: Errors during gene expression from DNA to proteins via transcription and translation may be deleterious for the functional maintenance of cells. In this paper, extensive genetic studies of the misreading of a GA repeat introduced into the lacZ gene of Escherichia coli indicate that in this bacteria, errors occur predominantly by a +2 translational frameshift, which is controlled by a tRNA modification involving the MnmE and GidA proteins. This ribosomal frameshift results from the coincidence of three events: (1) decreased codon-anticodon affinity at the P-site, which is caused by tRNA hypomodification in mnmE(-) and gidA(-) strains; (2) a repetitive mRNA sequence predisposing to slippage; and (3) increased translational pausing attributable to the presence of a rare codon at the A-site. Based on genetic analysis, we propose that GidA and MnmE act in the same pathway of tRNA modification, the absence of which is responsible for the +2 translational frameshift. The difference in the impact of the mutant gene on cell growth, however, indicates that GidA has at least one other function.
authors.affiliation: INSERM EPI9916, Faculté de Médecine Necker-Enfants Malades, 75730 Paris Cedex 15, France. bregeon@necker.fr
authors.forename: D
authors.initials: D
authors.lastname: Brégeon
authors.forename: V
authors.initials: V
authors.lastname: Colot
authors.forename: M
authors.initials: M
authors.lastname: Radman
authors.forename: F
authors.initials: F
authors.lastname: Taddei
mesh_terms: D020418:Algal Proteins / Q000378:metabolism; D001089:Arabinose / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division; D003062:Codon; D004251:DNA Transposable Elements / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D016368:Frameshift Mutation; D017930:Genes, Reporter; D005838:Genotype; D007763:Lac Operon; D008956:Models, Chemical; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010641:Phenotype; D010940:Plant Proteins; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013891:Thiouridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D020418:Algal Proteins; D003062:Codon; D004251:DNA Transposable Elements; D010940:Plant Proteins; D013891:Thiouridine; C011916:5-methylaminomethyl-2-thiouridine; D012343:RNA, Transfer; D001089:Arabinose; D001616:beta-Galactosidase