Import of human miRNA-RISC complex into Plasmodium falciparum and regulation of the parasite gene expression

During its life cycle, the malarial parasite Plasmodium goes through different asexual stages in human blood, and asexual and sexual stage in mosquito. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that post-transcriptional regulation plays an important role in stage-specific gene expression. Although miRNA-mediated gene regulation has been well-established to function in post-transcriptional regulation in many eukaryotes, existence of such a phenomenon or the presence of miRNA-associated factors in Plasmodium remains unclear. A number of miRNAs are shown to be imported into Plasmodium falciparum from erythrocytes and role of these miRNAs is not understood. Here we show that human Argonaute 2 (hAgo2) a component of the miRISC complex is imported by P. falciparum. In the parasite hAgo2 exists as in a complex with specific human miRNAs like let-7a and miR15a which can potentially target the Plasmodium genes Rad54 and Lipid/sterol:H+ symporter respectively. We show that hAgo2 associates with Rad54, Lipid/sterol:H+ symporter and other P. falciparum transcripts. These results highlight the existence of a mechanism by which malarial parasite imports hAgo2-miRNA complex from the host cells to regulate its gene expression.