Comparative proteomics uncovers low asparagine insertion inPlasmodiumtRip-KO proteins

Abstract

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.

Plasmodium, the Apicomplexa Outlier When It Comes to Protein Synthesis

“…Several observations support the fact that the Plasmodium AIMP tRip, combined to one or both MSCs, is involved in the import of exogenous tRNAs inside the parasite, and that their import could compensate for the deficiency of some Plasmodium tRNAs. The deletion of the gene-encoding tRip not only leads to a reduction in overall protein synthesis, but also to a selective drop in asparagine-rich proteins in the parasite [14,17]. Moreover, the (human) tRNA Asn is one of the favorite binders of (P. falciparum) tRip, which increases its chances of import [43].…”

“…In Plasmodium, tRip is an AIMP like no other: it is an integral membrane protein anchored in the plasma membrane of the parasite [13,14]; it homodimerizes using an alternative interface, named 1 ′ [13,15,16]; and it allows the formation of two MSCs characterized by two different GST-like domain organizations [13]. Most importantly, tRip is involved in the import of exogenous (host) tRNAs into the parasite [14] and its deletion leads to low infectivity and translational efficiency, which especially affects asparagine-rich proteins [17]. To date, it has not been demonstrated that Apicomplexa other than Plasmodium import and use host tRNAs.…”