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

作者：Lee Jin Young; Kim Dae Gyu; Kim Byung Gyu; Yang Won Suk; Hong Jeena; Kang Taehee; Oh Young Sun; Kim Kyung Rok; Han Byung Woo; Hwang Byung Joon; Kang Beom Sik; Kang Mi Sun; Kim Myung Hee; Kwon Nam Hoon^*; Kim Sunghoon

来源：Journal of Cell Science, 2014, 127(19): 4234-4245.

DOI：10.1242/jcs.152470

• Cell protection
• ERK
• Methionyl-tRNA synthetase
• Misacylation
• Reactive oxygen species

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.

• 出版日期2014-10-1