The pseudo-dimeric tyrosyl-tRNA synthetase of T. brucei aminoacylates cytosolic and mitochondrial tRNATyr and requires both monomeric units for activity

Abstract Aminoacyl-tRNA synthetases are essential for protein synthesis. The single-copy tyrosyl-tRNA synthetase ( Tb- TyrRS) of T. brucei has an unusual structure and forms a pseudo-dimer. It is therefore twice the size than tyrosyl-tRNA synthetases of most other organisms. Here we show by inducible RNAi that Tb- TyrRS is essential for normal growth of procyclic T. brucei . Furthermore we demonstrate that Tb- TyrRS aminoacylates cytosolic as well as mitochondrial tRNA Tyr indicating that it is dually localized. Finally we show that individual deletion of the 36 N- or C-terminal amino acids abolishes the function of Tb- TyrRS. This indicates that both monomeric units of the enzyme, the C-terminal one of which is predicted to lack enzymatic activity, are essential for Tb- TyrRS function. In summary our results together with previous studies support the notion that Tb- TyrRS might be a suitable drug target.