Aminoacyl-tRNA synthetase - a molecular multitasker

Aminoacyl-tRNA synthetases (AaRSs) are valuable "housekeeping" enzymes that ensure the accurate transmission of genetic information in living cells, where they aminoacylated tRNA molecules with their cognate amino acid and provide substrates for protein biosynthesis. In addition to their translational or canonical function, they contribute to nontranslational/moonlighting functions, which are mediated by the presence of other domains on the proteins. This was supported by several reports which claim that AaRS has a significant role in gene transcription, apoptosis, translation, and RNA splicing regulation. Noncanonical/ nontranslational functions of AaRSs also include their roles in regulating angiogenesis, inflammation, cancer, and other major physio-pathological processes. Multiple AaRSs are also associated with a broad range of physiological and pathological processes; a few even serve as cytokines. Therefore, the multifunctional nature of AaRSs suggests their potential as viable therapeutic targets as well. Here, our discussion will encompass a range of noncanonical functions attributed to Aminoacyl-tRNA Synthetases (AaRSs), highlighting their links with a diverse array of human diseases. AaRSs perform multiple essential roles in the cell. This class of enzymes are well studied for their canonical function, which is charging tRNA with its cognate amino acid. However, they are capable of a broad repertoire of functions that impact protein synthesis and extend to several other critical cellular activities such as tissue regeneration, angiogenesis, apoptosis, transcriptional and translational regulation. These novel activities affirm the family of AaRSs as a potential therapeutic target.image