Aminoacyl-tRNA synthetases, therapeutic targets for infectious diseases

Abstract

Despite remarkable advances in medical science, infection-associated diseases remain among the leading causes of death worldwide. There is a great deal of interest and concern at the rate at which new pathogens are emerging and causing significant human health problems. Expanding our understanding of how cells regulate signaling networks to defend against invaders and retain cell homeostasis will reveal promising strategies against infection. It has taken scientists decades to appreciate that eukaryotic aminoacyl-tRNA synthetases (ARSs) play a role as global cell signaling mediators to regulate cell homeostasis, beyond their intrinsic function as protein synthesis enzymes. Recent discoveries revealed that ubiquitously expressed standby cytoplasmic ARSs sense and respond to danger signals and regulate immunity against infections, indicating their potential as therapeutic targets for infectious diseases. In this review, we discuss ARS-mediated anti-infectious signaling and the emerging role of ARSs in antimicrobial immunity. In contrast to their ability to defend against infection, host ARSs are inevitably co-opted by viruses for survival and propagation. We therefore provide a brief overview of the communication between viruses and the ARS system. Finally, we discuss encouraging new approaches to develop ARSs as therapeutics for infectious diseases.

Keywords: Aminoacyl-tRNA synthetase; Antibiotics; Antiviral immunity; Infection; Multi-tRNA synthetase complex.

Graphical abstract

Fig. 1

Immune functions of ARSs. Viral infection releases EPRS from the MSC to exert antiviral activity by inhibiting MAVS degradation by PCBP2. AIMP1 also promotes antiviral immunity by potentiating the link between innate and adaptive immunity. WRS is secreted after bacteria or virus infection that subsequently primes innate immunity via binding to TLR4. Secreted cytokine-like ARSs are displayed with cognate stimuli. Each ARS function is represented by arrows in different colors. See text for details.