Ancestral AlaX Editing Enzymes for Control of Genetic Code Fidelity are not tRNA Specific [RNA]
February 27th, 2015 by Novoa, E. M., Vargas-Rodriguez, O., Lange, S., Goto, Y., Suga, H., Musier-Forsyth, K., Ribas de Pouplana, L.
Accurate protein synthesis requires the hydrolytic editing of tRNAs incorrecty aminoacylated by aminoacyl-tRNA synthetases (ARSs). Recognition of cognate tRNAs by ARS is less error-prone than amino acid recognition and, consequently, editing domains are generally believed to act only on the tRNAs cognate to their related ARSs. For example, the AlaX family of editing domains, including the editing domain of alanyl-tRNA synthetase and the related free-standing trans-editing AlaX enzymes, are thought to specifically act on tRNAAla, whereas the editing domains of threonyl-tRNA synthetases are specific for tRNAThr. Here we show that, contrary to this belief, AlaX-S, the smallest of extant AlaX enzymes, deacylates Ser-tRNAThr in addition to Ser-tRNAAla, and that a single residue is important to determine this behaviour. Our data indicates that promiscuous forms of AlaX are ancestral to tRNA-specific AlaXs. We propose that former AlaX domains were used to maintain translational fidelity in earlier stages of genetic code evolution when mis-serylation of several tRNAs was possible.