title: Imbalance of tRNA(Pro) isoacceptors induces +1 frameshifting at near-cognate codons.
abstract: Increased expression of the CCU/CCA/CCG-decoding tRNA(Pr)(o)3 on a multicopy plasmid leads to suppression of several +1 frameshift mutations in Salmonella enterica serovar Typhimurium. Systematic analysis of the site of frameshifting indicates that excess tRNA(Pr)(o)3 promotes near-cognate decoding at CCC codons. Re-phasing of the reading frame can be achieved by a subsequent slippage of the tRNA onto a cognate codon in the +1 reading frame. Frameshifting appears to be due to an imbalance of CCC-cognate and near-cognate tRNAs, as the effect of excess tRNA(Pr)(o)3 on reading frame maintenance can be reversed by increasing simultaneously the concentration of the cognate tRNA(Pr)(o)2. Finally, the cmo5U modification present at position 34 of tRNA(Pr)(o)3, which allows this tRNA to decode CCU in addition to CCG and CCA, also affects frameshifting, indicating that the ability of the near-cognate tRNA to decode a cognate codon efficiently in the alternative reading frame is important for re-phasing of the reading frame.
authors.affiliation: J. W. Wilson Laboratory, Department of Molecular and Cellular Biology and Biochemistry, 69 Brown Street, Brown University, Providence, RI 02912, USA. michael_o'connor@brown.edu
authors.forename: Michael
authors.initials: M
authors.lastname: O'Connor
mesh_terms: D000429:Alcohol Oxidoreductases; D000926:Anticodon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D003062:Codon / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics; D018965:Frameshifting, Ribosomal; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D011392:Proline / Q000235:genetics; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012361:RNA, Transfer, Pro / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics*; D013489:Suppression, Genetic / Q000235:genetics; D000637:Transaminases / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000926:Anticodon; D001426:Bacterial Proteins; D003062:Codon; D012329:RNA, Bacterial; D012361:RNA, Transfer, Pro; D011392:Proline; D000429:Alcohol Oxidoreductases; C021358:histidinol dehydrogenase; D000637:Transaminases; C053430:histidinol-phosphate aminotransferase; D001616:beta-Galactosidase