Apicomplexa -specific tRip facilitates import of exogenous tRNAs into malaria parasites

Abstract

The malaria-causing Plasmodium parasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylum Apicomplexa, have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene in Apicomplexa with a coding sequence for membrane-docking and structurespecific tRNA binding. This Apicomplexa protein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs. Plasmodium is thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.tRNA | Plasmodium | trafficking

Nuclear, Cytosolic, and Surface-Localized Poly(A)-Binding Proteins of Plasmodium yoelii

“…These data directly support our previous proteomic labeling experiments performed with P. falciparum salivary gland sporozoites that robustly showed that PfPABP1 is surface exposed ( 33 ). Moreover, this is the third RNA-binding protein known to localize on the surface of sporozoites, as tRip and GAPDH were also recently found to localize on the surface as well ( 34 , 41 ). Taking the results together, we found that PyPABP1 is localized in the cytosol and nuclear periphery throughout the sexual and asexual blood stages but becomes surface localized and is shed by salivary gland sporozoites during gliding motility.…”

OB or Not OB: Idiosyncratic utilization of the tRNA‐binding OB‐fold domain in unicellular, pathogenic eukaryotes

“…However, new functions have arisen in unicellular eukaryotes. For example, in Plasmodium , the GST fusion in tRip is localized in the parasite membrane and is involved in tRNA trafficking . The Yip1‐OB fusion present in P .…”

“…However, new functions have arisen in unicellular eukaryotes. For example, in Plasmodium, the GST fusion in tRip is localized in the parasite membrane and is involved in tRNA trafficking [37]. The Yip1-OB fusion present in P. aphanidermatum is another example of a possible membrane protein with an OB-fold tRNA-binding domain, of unknown function in this case.…”

“…Plasmodium , which causes malaria, is representative of this group and they require two different hosts (insects and mammals). In Plasmodium , the tRNA import protein tRip is an Arc1p homolog . In vitro , tRip binds human tRNA species with high affinity ( K D = 5–10 n m ) and recognizes the elbow of the molecule via its C‐terminal OB‐fold.…”

Pathways to disease from natural variations in human cytoplasmic tRNAs

“…Unicellular protozoans encode near the theoretical minimum of tRNA genes, such as the malaria parasite Plasmodium falciparum, which has only 35 tRNA genes (43). P. falciparum was recently found to import additional tRNAs from its host (44). Some species of fish have astoundingly high tRNA gene numbers (Table S2), such as the elephant shark (Callorhinchus milii), which encodes 13,724 tRNAs (43).…”