Trends in Parasitology
Volume 27, Issue 10, October 2011, Pages 467-476
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Review
Protein translation in Plasmodium parasites

https://doi.org/10.1016/j.pt.2011.05.005Get rights and content

The protein translation machinery of the parasite Plasmodium is the target of important anti-malarial drugs, and encompasses many promising targets for future drugs. Plasmodium parasites have three subcellular compartments that house genomes; the nucleus, mitochondrion and apicoplast, and each requires its own compartmentalized transcription and translation apparatus for survival. Despite the availability of the complete genome sequence that should reveal the requisite elements for all three compartments, our understanding of the translation machineries is patchy. We review what is known about cytosolic and organellar translation in Plasmodium and discuss the molecules that have been identified through genome sequencing and post-genomic analysis. Some translation components are yet to be found in Plasmodium, whereas others appear to be shared between translationally active organelles.

Section snippets

Plasmodium translation in the post-genomic era

Since the sequencing of the P. falciparum genome, and the complete or near-complete genome sequencing of a handful of other Plasmodium species, there have been tremendous advances in the characterization of the molecules governing host–pathogen interactions. Less striking has been the pursuit in Plasmodium species of one of the basic processes of life – the translation of RNA into protein. Perhaps the very centrality of this process to biology has made it a less attractive research topic in a

Three compartments, three translation machines?

Plasmodium, as do plants, algae, and the majority of other Apicomplexans, possesses three active compartments of translation: the cytosol, mitochondrion and a relic plastid termed the apicoplast (see Glossary) or apicomplexan plastid. Apicomplexans contain, therefore, a mixture of translation machinery, with eukaryotic components for cytosolic mRNA translation and prokaryotic-like components for mRNA translation in the mitochondria and apicoplast. The apicoplast is non-photosynthetic and

Amino acids

P. falciparum parasites have multiple means of obtaining amino acids for protein synthesis, but the most important for growth in vivo remain unclear. Of the 20 canonical amino acids, Plasmodium possesses biosynthetic pathways for Asn, Gln, Gly, Pro, Asp and Glu [14]. However, very low amounts of these amino acids are incorporated into Plasmodium proteins [15]. This limited capacity for de novo amino acid synthesis means that, during in vitro culture at least, to charge its own tRNAs Plasmodium

tRNA

Of the three Plasmodium genomes, nuclear, apicoplast and mitochondrial, only the first two encode tRNAs 3, 26, 27 and correspond to compartments in which translation has been demonstrated [5]. A total of 46 tRNA genes, coding for 45 tRNA isoacceptors (initiator and elongator tRNAMet are encoded by two different genes), are found in the nuclear genome whereas the apicoplast genome contains 35 genes encoding 26 tRNA isoacceptors. With the exception of the apicoplast initiator tRNAMet,

Control and regulation of translation

A large number of proteomic studies have examined individual life stages of Plasmodium, or compared transitions from one stage to another (reviewed in [65]). Although these studies show shifts in protein composition between stages or treatments, the lack of corresponding transcriptome analyses for the same parasites makes it unclear whether expression regulation takes place at the transcriptional, translational or post-translational levels. The earliest mRNA microarrays indicate that the timing

Drug targets

Translation is a longstanding and major focus for drug development in Plasmodium. The relevant enzymes in the apicoplast and mitochondria in particular are attractive targets for malaria chemotherapy due to their prokaryotic origin. The promise of anti-translation inhibitors as antimalarials is highlighted by the number of inhibitors of protein translation already used for the clinical treatment of malaria (Table 3), of which doxycycline is perhaps the most widely known. Despite its potency and

Unanswered questions

Plasmodium has three translationally active compartments, the nucleus, apicoplast and mitochondrion, each with distinct evolutionary origins. These origins are reflected in differing mechanisms controlling translation, presenting three separate biological stories, and three potential sets of targets for inhibition. Several aspects of these stories remain to be revealed: ribosomal proteins for each compartment are generally poorly annotated, and the recent structural elucidation of ribosomes in

Acknowledgments

The authors are funded by an European Union FP7 Collaborative Project Grant HEALTH-F3-2009-223024 – Mephitis. S.A.R. is funded by Australian Research Council Future fellowship FT0990350. The authors acknowledge and apologize to the authors of many important studies in this field whose findings had to be omitted or referred to only via review papers owing to space constraints.

Glossary

Apicoplast
non-photosynthetic plastid with its own circular genome, found in most Apicomplexa. Arose via secondary endosymbiosis.
Cytosol
the intracellular fluid found within cells, excluding that within membrane-bound organelles.
Isoacceptors
tRNAs that have different anticodons but are charged with the same amino acid.
Mitochondrion
endosymbiotic organelle with its own small mitochondrial chromosome. Generally plays a major role in energy conversion.
Peptide exit tunnel
the site, formed by proteins

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