A crucial role of the zinc finger protein PfZnFP-G in sexual differentiation of the malaria parasites, Plasmodium falciparum

We described the biological role of a putative zinc finger protein (Plasmodb id: PF3D7_1008600), which plays an important role during the initiation and subsequent progression of gametocytogenesis in P. falciparum. Hence we termed the protein P. falciparum Zinc Finger Protein for Gametocytogenesis (PfZnFP-G). During the asexual intraerythrocyic developmental cycle (IDC), PfZnFP-G levels peak during the schizont stage during which it is localized in the nucleus. During the IDC, PfZnFP-G appears to be stochastically expressed in ~3% parasite population. Deactivation of PfZnFP-G appears to suppress, but not fully inhibit, production of gametocytes and vice versa overproduction of PfZnFP-G stimulates gametocytogenesis. In addition, PfZnFP-G is capable of associating with DNA binding preferentially to intergenic, promoter regions of the genome, and this binding correlates positively with transcription, particularly of other gametocyte specific genes. PfZnFP-G is also expressed in the mid-to-late gametocytes where it is present in the cytoplasm. Overall, these results suggest a dual function of PfZnFP-G in gametocytogenesis including: (i) commitment as a transcription factor and (ii) gametocyte maturation as a putative RNA binding protein. Transgenic 3D7 wild type parasite lines were generated with PfZnFP-G tagged, over-expressed and knocked-out. Transcriptional profiles across the parasite life cycle were generated. Genome occupancy of PfZnFP-G were also investigated and compared to the corresponding transcriptional profiles.