Phenylalanyl-tRNA synthetase editing defects result in efficient mistranslation of phenylalanine codons as tyrosine

RNA. 2007 Nov;13(11):1881-6. doi: 10.1261/rna.684107. Epub 2007 Sep 5.


Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs by elongation factor Tu (EF-Tu) and the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but is able to correct the mistake using a proofreading activity named editing. Previously we found that overproduction of editing-defective PheRS resulted in Tyr incorporation at Phe-encoded positions in vivo, although the misreading efficiency could not be estimated. This raised the question as to whether or not EF-Tu and the ribosome provide further proofreading mechanisms to prevent mistranslation of Phe codons by Tyr. Here we show that, after evading editing by PheRS, Tyr-tRNA(Phe) is recognized by EF-Tu as efficiently as the cognate Phe-tRNA(Phe). Kinetic decoding studies using full-length Tyr-tRNA(Phe) and Phe-tRNA(Phe), as well as a poly(U)-directed polyTyr/polyPhe synthesis assay, indicate that the ribosome lacks discrimination between Tyr-tRNA(Phe) and Phe-tRNA(Phe). Taken together, these data suggest that PheRS editing is the major proofreading step that prevents infiltration of Tyr into Phe codons during translation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Codon / metabolism*
  • Peptide Chain Elongation, Translational*
  • Peptide Elongation Factor Tu / metabolism
  • Phenylalanine / metabolism*
  • Phenylalanine-tRNA Ligase / metabolism*
  • RNA Editing / physiology*
  • RNA, Transfer, Amino Acyl / metabolism
  • Time Factors
  • Tyrosine / metabolism*


  • Codon
  • RNA, Transfer, Amino Acyl
  • Tyrosine
  • Phenylalanine
  • Peptide Elongation Factor Tu
  • Phenylalanine-tRNA Ligase