A dual-targeted aminoacyl-tRNA synthetase in Plasmodium falciparum charges cytosolic and apicoplast tRNA(Cys)

作者：Pham James S; Sakaguchi Reiko; Yeoh Lee M; De Silva Nilushi S; McFadden Geoffrey I; Hou Ya Ming; Ralph Stuart A^*

来源：Biochemical Journal, 2014, 458(3): 513-523.

DOI：10.1042/BJ20131451

• alternative splicing
• aminoacylation
• aminoacyl-tRNA synthetase
• apicoplast
• Apicomplexa
• dual-targeted
• Plasmodium
• Toxoplasma gondii
• trafficking
• tRNA

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. In the present study we investigate how the parasite manages these translational requirements for charged tRNA(Cys) with only a single gene for CysRS (cysteinyl-tRNA synthetase). We demonstrate that the single PfCysRS (Plasmodium falciparum CysRS) transcript is alternatively spliced, and, using a combination of endogenous and heterologous tagging experiments in both R falciparum and Toxoplasma gondii, we show that CysRS isoforms traffic to the cytosol and apicoplast. PfCysRS can recognize and charge the eukaryotic tRNA(Cys) 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. The results of the present study indicate that apicomplexan parasites have lost their original plastidic cysteinyl-tRNA synthetase, and have replaced it with a dual-targeted eukaryotic type CysRS that recognizes plastid and nuclear tRNA(Cys). 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.

• 出版日期2014-3-15