Aminoacyl-tRNA synthetases beyond decoding

Translation of messenger RNA (mRNA) into proteins is central to all life and of high therapeutic relevance. Aminoacyl-tRNA synthetases assign the correct amino acid to transfer-RNA (tRNA), thereby linking the information encoded in nucleic acids to building blocks for protein synthesis. I describe how a protein complex formed by aminoacyl-tRNA synthetases does not support their enzymatic functions, but instead ensures correct localization within the mammalian cell, with possible relevance for neurodevelopmental disorders. Levels of an aminoacyl-tRNA synthetase in the cell nucleus are responsive to metabolic modulation of its corresponding amino acid, which drops during disease states. In the cell nucleus, the tRNA synthetase sequesters an mRNA processing factor that modulates nuclear compartmentalization. By hindering the mobility of its interaction partner, the tRNA synthetase controls protein isoform preferences and ultimately communication with immune cells during inflammatory states.