Severe oxidative stress induces protein mistranslation through impairment of an aminoacyl-tRNA synthetase editing site

Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4028-33. doi: 10.1073/pnas.1000315107. Epub 2010 Feb 16.

Abstract

Oxidative stress arises from excessive reactive oxygen species (ROS) and affects organisms of all three domains of life. Here we present a previously unknown pathway through which ROS may impact faithful protein synthesis. Aminoacyl-tRNA synthetases are key enzymes in the translation of the genetic code; they attach the correct amino acid to each tRNA species and hydrolyze an incorrectly attached amino acid in a process called editing. We show both in vitro and in vivo in Escherichia coli that ROS reduced the overall translational fidelity by impairing the editing activity of threonyl-tRNA synthetase. Hydrogen peroxide oxidized cysteine182 residue critical for editing, leading to Ser-tRNA(Thr) formation and protein mistranslation that impaired growth of Escherichia coli. The presence of major heat shock proteases was required to allow cell growth in medium containing serine and hydrogen peroxide; this suggests that the mistranslated proteins were misfolded.

Publication types

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

MeSH terms

  • Amino Acyl-tRNA Synthetases / chemistry
  • Amino Acyl-tRNA Synthetases / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Oxidative Stress*
  • Protein Biosynthesis*
  • RNA Editing*
  • beta-Lactamases / genetics

Substances

  • beta-Lactamases
  • Amino Acyl-tRNA Synthetases