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

Aminoacyl-tRNA synthetases (AARSs) play an indispensable role in the translation of mRNAs into proteins. It has become amply clear that AARSs also have non-canonical or non-translational, yet essential, functions in a myriad of cellular and developmental processes. In this mini-review we discuss the current understanding of the roles of threonyl-tRNA synthetase (TARS) beyond protein synthesis and the underlying mechanisms. The two proteins in eukaryotes — cytoplasmic TARS1 and mitochondrial TARS2 — exert their non-canonical functions in the regulation of gene expression, cell signaling, angiogenesis, inflammatory responses, and tumorigenesis. The TARS proteins utilize a range of biochemical mechanisms, including assembly of a translation initiation complex, unexpected protein–protein interactions that lead to activation or inhibition of intracellular signaling pathways, and cytokine-like signaling through cell surface receptors in inflammation and angiogenesis. It is likely that new functions and novel mechanisms will continue to emerge for these multi-talented proteins.