Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for protein synthesis with evolutionarily conserved enzymatic mechanisms. Despite their similarity across organisms, scientists have been able to generate effective anti-infective agents based on the structural differences in the catalytic clefts of ARSs from pathogens and humans. However, recent genomic, proteomic and functionomic advances have unveiled unexpected disease-associated mutations and altered expression, secretion and interactions in human ARSs, revealing hidden biological functions beyond their catalytic roles in protein synthesis. These studies have also brought to light their potential as a rich and unexplored source for new therapeutic targets and agents through multiple avenues, including direct targeting of the catalytic sites, controlling disease-associated protein–protein interactions and developing novel biologics from the secreted ARS proteins or their parts. This Review addresses the emerging biology and therapeutic applications of human ARSs in diseases including autoimmune and rare diseases, and cancer.
Bibliographical noteFunding Information:
This work was supported by NRF-M3A6A4-2010-0029785 (S.K.), NRF-2015M3A6A4065724 (N.H.K.) and NRF-2017M3A9F7079378 (N.H.K.) from the National Research Foundation, the Ministry of Science and ICT (MSIT) of Korea and by the US National Institutes of Health (NIH) P01 HL029582 (P.L.F.). The authors thank B. S. Kang (Kyungbuk University) for drawing the architecture of class I and class II catalytic sites. They also thank J. Y. Lee (Buck Institute) for collecting data for secreted ARSN in human body fluids.
All Science Journal Classification (ASJC) codes
- Drug Discovery