An Important Role for the Multienzyme Aminoacyl-tRNA Synthetase Complex in Mammalian Translation and Cell Growth

SummaryIn mammalian cells, aminoacyl-tRNA synthetases (aaRSs) are organized into a high-molecular-weight multisynthetase complex whose cellular function has remained a mystery. In this study, we have taken advantage of the fact that mammalian cells contain two forms of ArgRS, both products of the same gene, to investigate the complex's physiological role. The data indicate that the high-molecular-weight form of ArgRS, which is present exclusively as an integral component of the multisynthetase complex, is essential for normal protein synthesis and growth of CHO cells even when low-molecular-weight, free ArgRS is present and Arg-tRNA continues to be synthesized at close to wild-type levels. Based on these observations, we conclude that Arg-tRNA generated by the synthetase complex is a more efficient precursor for protein synthesis than Arg-tRNA generated by free ArgRS, exactly as would be predicted by the channeling model for mammalian translation.