A dual-targeted aminoacyl-tRNA synthetase in Plasmodium falciparum charges cytosolic and apicoplast tRNACys

Plasmodium parasites possess two endosymbiotic organelles: a mitochondrion, and a relict plastid called the apicoplast. To accommodate the translational requirements of these organelles in addition to its cytosolic translation apparatus, the parasite must maintain a supply of charged tRNA molecules in each of these compartments. Here we investigate how the parasite manages these translational requirements for charged tRNACys with only a single gene for cysteinyl-tRNA synthetase (CysRS). We demonstrate that the single PfCysRS transcript is alternatively spliced, and, using a combination of endogenous and heterologous tagging experiments in both P. falciparum and Toxoplasma gondii, we show that CysRS isoforms traffic to the cytosol and apicoplast. PfCysRS can recognise and charge the eukaryotic tRNACys encoded by the Plasmodium nucleus as well as the bacterial type tRNA encoded by the apicoplast genome, albeit with a preference for the eukaryotic type cytosolic tRNA. Our data indicate that apicomplexan parasites have lost their original plastidic cysteinyl-tRNA synthetase, and have replaced it with a dual-targeted eukaryotic type CysRS that recognises plastid and nuclear tRNACys. Inhibitors of the Plasmodium dual-targeted CysRS would potentially offer a therapy capable of the desirable immediate effects on parasite growth as well as the irreversibility of inhibitors that disrupt apicoplast inheritance.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research