Promiscuous methionyl-tRNA synthetase mediates adaptive mistranslation to protect cells against oxidative stress

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

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)


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 noncognate tRNAs with lower affinity for tRNAMet, 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.

Original languageEnglish
Pages (from-to)4234-4245
Number of pages12
JournalJournal of cell science
Issue number19
Publication statusPublished - 2014

Bibliographical note

Publisher Copyright:
© 2014. Published by The Company of Biologists Ltd.

All Science Journal Classification (ASJC) codes

  • Cell Biology


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