Phosphocode-dependent glutamyl-prolyl-tRNA synthetase 1 signaling in immunity, metabolism, and disease

Abstract

Ubiquitously expressed aminoacyl-tRNA synthetases play essential roles in decoding genetic information required for protein synthesis in every living species. Growing evidence suggests that they also function as crossover mediators of multiple biological processes required for homeostasis. In humans, eight cytoplasmic tRNA synthetases form a central machinery called the multi-tRNA synthetase complex (MSC). The formation of MSCs appears to be essential for life, although the role of MSCs remains unclear. Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is the most evolutionarily derived component within the MSC that plays a critical role in immunity and metabolism (beyond its catalytic role in translation) via stimulus-dependent phosphorylation events. This review focuses on the role of EPRS1 signaling in inflammation resolution and metabolic modulation. The involvement of EPRS1 in diseases such as cancer is also discussed.

Beyond protein synthesis: non-translational functions of threonyl-tRNA synthetases

“…Indeed, there are numerous cases of non-translational functions involving the new domains of AARSs [ 8 , 9 ]. For example, the WHEP domain of WARS1 is involved in the activation of p53 in the nucleus, whereas the multiple WHEP domains in EPRS1 play a critical role in γ­interferon activated inhibition of translation (reviewed in [ 10 , 17 ]). Along with the emergence of the new domains in AARSs, higher eukaryotes evolved to have a multi-synthetase complex (MSC).…”