Promiscuous Methionyl-tRNA Synthetase Mediates Adaptive Mistranslation to Protect Cells Against Oxidative Stress

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2014 Aug 7

PMID 25097229

Citations 62

Authors

Jin Young Lee

Dae Gyu Kim

Byung-Gyu Kim

Won Suk Yang

Jeena Hong

Taehee Kang

Young Sun Oh

Kyung Rok Kim

Byung Woo Han

Byung Joon Hwang

Beom Sik Kang

Mi-Sun Kang

Myung-Hee Kim

Nam Hoon Kwon

Sunghoon Kim

Affiliations

Soon will be listed here.

Abstract

Aminoacyl-tRNA synthetases (ARSs) acylate transfer (t)RNAs with amino acids. Charging tRNAs with the right amino acids is the first step in translation; therefore, the accurate and error-free functioning of ARSs is an essential prerequisite for translational fidelity. A recent study found that methionine (Met) can be incorporated into non-Met residues of proteins through methionylation of non-cognate tRNAs under conditions of oxidative stress. However, it was not understood how this mis-methionylation is achieved. Here, we report that methionyl-tRNA synthetase (MRS) is phosphorylated at Ser209 and Ser825 by extracellular signal-related kinase (ERK1/2) under conditions of stress caused by reactive oxygen species (ROS), and that this phosphorylated MRS shows increased affinity for non-cognate tRNAs with lower affinity for tRNA(Met), leading to an increase in Met residues in cellular proteins. The expression of a mutant MRS containing the substitutions S209D and S825D, mimicking dual phosphorylation, reduced ROS levels and cell death. This controlled inaccuracy of MRS seems to serve as a defense mechanism against ROS-mediated damage at the cost of translational fidelity.

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