Aminoacyl-tRNA synthetases (aaRSs) are a family of essential enzymes that catalyze aminoacylation – ligation of amino acids to their cognate tRNAs, thus creating substrates for protein synthesis. These house-keeping proteins have emerged to have wide-ranging functions independent of their catalytic activity, from transcriptional regulation, nutrient sensing, to angiogenesis and myogenesis. Mutations in or dysregulation of aaRSs are associated with many human diseases including neuropathies, chronic inflammatory diseases, muscular dystrophy, and cancer. In recent years our lab has been interested in the non-translational functions of aaRSs in cell growth, muscle regeneration, and muscular dystrophy (DMD). The non-translational functions of aaRS can provide unique opportunities for therapeutic targeting.
M.-S. Yoon†, K. Son†, E. Arauz, J. M. Han, S. Kim, and J. Chen, (2016) Leucyl-tRNA synthetase activates Vps34 in amino acid-sensing mTORC1 signaling, Cell Rep 16, 1510-17. Link to article
K. Son, J.-S. You, M.S. Yoon, C. Dai, J.H. Kim, N. Khanna, A. Banerjee, S.A. Martinis, G. Han, J.M. Han, S. Kim, J. Chen, (2019) Nontranslational function of leucyl-tRNA synthetase regulates myogenic differentiation and skeletal muscle regeneration. J Clin Invest. 130, 2088-2093. Link to article
C. Dai, A Reyes-Ordonez, J.-S. You, and J. Chen, (2021) A non-translational role of threonyl-tRNA synthetase in regulating JNK signaling during skeletal myogenesis. FASEB J. 35, e21948. Link to article
P. Barai and J. Chen, (2024) Beyond protein synthesis: non-translational functions of threonyl-tRNA synthetases. Biochem. Soc. Trans., 52, 661. Link to article
J.-S. You, K. Karaman, A. Reyes-Ordoñez, S. Lee, Y. Kim, R. Bashir, and J. Chen, (2024) Leucyl-tRNA synthetase contributes to muscle weakness through mTORC1 activation and autophagy suppression in a mouse model of Duchenne Muscular Dystrophy. American Journal of Pathology, 194, 1571. Link to article