Functional Substitution of a Eukaryotic Glycyl-tRNA Synthetase with an Evolutionarily Unrelated Bacterial Cognate Enzyme

Two oligomeric types of glycyl-tRNA synthetase (GlyRS) are found in nature: a alpha(2) type and a alpha(2)beta(2) type. The former has been identified in all three kingdoms of life and often pairs with tRNA(Gly) that carries an A73 discriminator base, while the latter is found only in bacteria and chloroplasts and is almost always coupled with tRNA(Gly) that contains U73. In the yeast Saccharomyces cerevisiae, a single GlyRS gene, GRS1, provides both the cytoplasmic and mitochondrial functions, and tRNA(Gly) isoacceptors in both compartments possess A73. We showed herein that Homo sapiens and Arabidopsis thaliana cytoplasmic GlyRSs (both alpha(2)-type enzymes) can rescue both the cytoplasmic and mitochondrial defects of a yeast grs1(-) strain, while Escherichia coli GlyRS (a alpha(2)beta(2)-type enzyme) and A. thaliana organellar GlyRS (a (alpha beta)(2)-type enzyme) failed to rescue either defect of the yeast mull allele. However, a head-to-tail alpha beta fusion of E. coli GlyRS effectively supported the mitochondrial function. Our study suggests that a alpha(2)-type eukaryotic GlyRS may be functionally substituted with a alpha(2)beta(2)-type bacterial cognate enzyme despite their remote evolutionary relationships.