Aminoacyl-tRNA synthetases and translation machinery (aaRS/Translation Machinery)

Aminoacyl-tRNA synthetases (aaRSs) and the associated translation machinery constitute the fundamental apparatus for protein biosynthesis in all living organisms. The aaRS enzymes are responsible for the precise attachment of amino acids to their corresponding tRNA molecules, ensuring the high fidelity of the translation process (1). The broader translation machinery, including the ribosome and various initiation, elongation, and termination factors, then utilizes these aminoacylated tRNAs to assemble polypeptide chains based on mRNA templates (2). This system is a primary target for numerous classes of antibiotics and antifungals, which exploit structural differences between prokaryotic and eukaryotic components to achieve selective toxicity (3). For example, mupirocin and tavaborole target specific aaRS enzymes, while macrolides and aminoglycosides inhibit ribosomal function (4). Beyond infectious diseases, mutations or dysregulation within this machinery are implicated in various human pathologies, including Charcot-Marie-Tooth disease, anti-synthetase syndrome, and several types of cancer (5). Consequently, this machinery is increasingly being explored for the development of novel therapeutics in oncology and rare genetic disorders, moving beyond its traditional role in antimicrobial development (6).

Other names

tRNA-ligasesAminoacyl-tRNA ligasesTranslational apparatusProtein synthesis machineryRibosome and translation factors

Inhibition of aminoacyl-tRNA synthesis (competitive or non-competitive), disruption of ribosomal subunit function (30S or 50S), and interference with translation initiation, elongation, or translocation.