An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA.

Aminoacyl tRNA therefore plays an important role in RNA translation, the expression of genes to create proteins.

The synthetase first binds ATP and the corresponding amino acid (or its precursor) to form an aminoacyl-adenylate, releasing inorganic pyrophosphate (PPi).

The accuracy of aminoacyl-tRNA synthetase is so high that it is often paired with the word "superspecificity” when it is compared to other enzymes that are involved in metabolism.

Although not all synthetases have a domain with the sole purpose of editing, they make up for it by having specific binding and activation of their affiliated amino acids.

[9] Aminoacyl-tRNA synthetases have been kinetically studied, showing that Mg2+ ions play an active catalytic role and therefore aaRs have a degree of magnesium dependence.

That is, they violate the so-called canonical phylogenetic pattern shown by most other enzymes for the three domains of life - Archaea, Bacteria, and Eukarya.

[13] A widespread belief in the evolutionary stability of this superfamily, meaning that every organism has all the aaRSs for their corresponding amino acids, is misconceived.

There exists a theory that the increasing number of aaRSs that add domains is due to the continuous evolution of higher organisms with more complex and efficient building blocks and biological mechanisms.

[16] As genetic efficiency evolved in higher organisms, 13 new domains with no obvious association with the catalytic activity of aaRSs genes have been added.

[17] Another use is introducing amino acids bearing reactive functional groups for chemically modifying the target protein.

Certain diseases’ causation (such as neuronal pathologies, cancer, disturbed metabolic conditions, and autoimmune disorders) have been correlated to specific mutations of aminoacyl-tRNA synthetases.

[18] Diabetes, a metabolic disease, induces oxidative stress, which triggers a build up of mitochondrial tRNA mutations.

[24] Findings beginning in 1999 and later revealed a previously unrecognized layer of biology: these proteins control gene expression within the cell of origin, and when released exert homeostatic and developmental control in specific human cell types, tissues and organs during adult or fetal development or both, including pathways associated with angiogenesis, inflammation, the immune response, the mechanistic target of rapamycin (mTOR) signalling, apoptosis, tumorigenesis, and interferon gamma (IFN-γ) and p53 signalling.

It was shown that CMT-mutant glycyl-tRNA synthetase variants are still able to bind tRNA-gly but fail to release it, leading to depletion of the cellular pool of glycyl-tRNA-gly, what in turn results in stalling of the ribosome on glycine codons during mRNA translation.