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

• Published in: Experimental & molecular medicine 2023, 55(0), , pp.2116-2126
• Main Authors: Lee, Eun-Young, Hwang, Jungwon, Kim, Myung Hee
• Format: Article
• Language: English
• Subjects: 13/95; 631/337; 631/45; 96; Amino Acyl-tRNA Synthetases - genetics; Amino Acyl-tRNA Synthetases - metabolism; Biomedical and Life Sciences; Biomedicine; Enzymes; Homeostasis; Humans; Immune response; Immunity; Immunity (Disease); Inflammation; Inflammatory diseases; Lipid metabolism; Medical Biochemistry; Metabolism; Molecular Medicine; Phosphorylation; Proline-tRNA ligase; Protein Binding; Protein biosynthesis; Protein synthesis; Protein turnover; Review; Review Article; RNA viruses; RNA, Transfer - metabolism; Stem Cells; Therapeutic targets; Transfer RNA; Translation; tRNA; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-01094-x

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. EPRS1 signaling: a key player in immunity and metabolism EPRS1, a vital enzyme for protein synthesis, has been found to play a significant role in various biological processes beyond translation. Researchers have discovered that EPRS1 can act as a molecular switch, regulating inflammation, metabolism, and disease. The enzyme’s phosphorylation at specific sites allows it to dissociate from the multi-tRNA synthetase complex (MSC) and interact with different proteins to perform various functions. For example, EPRS1 regulates inflammation resolution in response to LPS and bacteria, adipocyte lipid metabolism in response to insulin, and antiviral immune function in response to RNA viruses. These findings highlight the potential of EPRS1 as a therapeutic target for treating inflammatory diseases, obesity, aging, and viral infections. Further research is needed to better understand the mechanisms underlying EPRS1’s diverse functions and develop targeted therapies.