Disease association and therapeutic routes of aminoacyl-tRNA synthetases

Aminoacyl-tRNA synthetases (ARSs) are enzymes that catalyze the ligation of amino acids to tRNAs for translation. Beyond their traditional role in translation, ARSs have acquired regulatory functions in various biological processes (epi-translational functions). With their dual-edged activities, aberrant expression, secretion, and mutations of ARSs are associated with human diseases, including cancer, autoimmune diseases, and neurological diseases. The increasing numbers of newly unveiled activities and disease associations of ARSs have spurred interest in novel drug development, targeting disease-related catalytic and noncatalytic activities of ARSs as well as harnessing ARSs as sources for biological therapeutics. This review speculates how the translational and epi-translational activities of ARSs can be related and describes how their activities can be linked to diseases and drug discovery.