Comparative proteomics uncovers correlation between tRip-mediated host tRNA import and asparagine insertion in Plasmodium proteins

tRNAs are not only essential for decoding the genetic code, but their abundance also has a strong impact on the rate of protein production, folding, and on the stability of their encoding messenger RNAs. Plasmodium expresses a unique surface protein called tRip, involved in the import of exogenous tRNAs into the parasite. Comparative proteomic analysis of the blood stage of wild-type and tRip-KO variant of P. berghei parasites revealed that down-regulated proteins in the mutant parasite are distinguished by a bias in their asparagine content. We therefore propose a model in which a dynamic import of host tRNAAsn allows the synthesis of asparagine-rich regulatory proteins that efficiently and selectively control the parasite infectivity. These results suggest a novel mechanism of translational control where import of host tRNAs emerge as critical regulator of gene expression in the Plasmodium developmental cycle and pathogenesis. Significance Statement tRip is a surface protein involved in the import of exogenous tRNAs into the malaria parasite, Plasmodium. To better understand tRNA import and protein synthesis in Plasmodium, the proteomes of wild-type and tRip-KO parasites were compared. Most of the proteins deregulated in the tRip-KO parasite were under expressed compared to the wild-type. Asparagine usage was greatly increased in the proteins that were down-regulated in the tRip-KO, suggesting that the mutated parasite is impaired in inserting asparagine into proteins. Moreover, the presence of host tRNAs inside the blood stage parasite and the possibility of charging these imported tRNAs with endogenous aminoacyl-tRNA synthetases, led us to propose that, imported host tRNAs participate in parasite protein synthesis and control its development.