Translational misreading: a tRNA modification counteracts a+2 ribosomal frameshift

Errors during gene expression from DNA to proteins via transcription and tr anslation may be deleterious for the functional maintenance of cells. In th is paper, extensive genetic studies of the misreading of a GA repeat introd uced into the lacZ gene of Escherichia coli indicate that in this bacteria, errors occur predominantly by a +2 translational frameshift, which is cont rolled by a tRNA modification involving the MnmE and GidA proteins. This ri bosomal frameshift results from the coincidence of three events: (1) decrea sed codon-anticodon affinity at the P-site, which is caused by tRNA hypomod ification in mnmE(-) and gidA(-) strains; (2) a repetitive mRNA sequence pr edisposing to slippage, and (3) increased translational pausing attributabl e to the presence of a rate 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, in dicates that GidA has at least one other function.