Abstract
Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present for the import of lysyl tRNA in yeast.
Highlights
Aminoacyl-tRNA synthetases are a heterogeneous family of enzymes responsible for aminoacylating tRNAs with the appropriate amino acids
We show here that human mitochondrial lysyl tRNA-synthetase (KARS) cDNA, when present in multiple copies, partially rescues the growth defect of msk1D cells on non-fermentable carbon sources
We show that human Kars imports tRK1 into isolated yeast and mammalian mitochondria in the presence of yeast or human cytosolic factors
Summary
Aminoacyl-tRNA synthetases are a heterogeneous family of enzymes responsible for aminoacylating tRNAs with the appropriate amino acids. The budding yeast, Saccharomyces cerevisiae, contains two sets of lysyl-tRNA synthetases (Msk and Krs1) that are encoded by nuclear DNA. The imported tRK1 that was mutagenized to alter amino acid specificity was functional in yeast mitochondrial translation both in vivo and in vitro [5]. For tRK1 to be eligible for mitochondrial import, it has to go through a complex set of reactions that includes aminoacylation of tRK1 by cytosolic lysyl-tRNA synthetase, interaction of tRK1 with glycolytic enzyme enolase 2 (Eno2) and binding to the precursor form of Msk (pre-Msk1) [3,6,7]. The translocation across the mitochondrial membranes requires intact protein import machinery, ATP and additional unidentified cytosolic factors. The utilization of tRK1 in mitochondria is dependent on continuous action of cytosolic and mitochondrial tRNA synthetases. The utilization of imported tRK1 is limited by the activity and availability of these two synthetases besides its function being restricted to one round of translation
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