Severe oxidative stress induces protein mistranslation through impairment of an aminoacyl-tRNA synthetase editing site.
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.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
Jiqiang
J
Ling
Dieter
D
Söll
D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D017393:RNA Editing; D001618:beta-Lactamases / Q000235:genetics
D001618:beta-Lactamases; D000604:Amino Acyl-tRNA Synthetases