The Plasmodium falciparum CCCH zinc finger protein ZNF3 is an RNA-binding protein important for gametocyte maturation and transmission to the mosquito

Abstract text

CCCH-type zinc finger proteins represent a family of RNA-binding proteins with regulatory functions in mRNA processing. Previously, we identified a Plasmodium falciparum CCCH-zinc finger protein, here named ZNF3 (PF3D7_0315600), which was significantly up-regulated in its transcript levels following treatment of gametocytes with the histone deacetylase inhibitor Trichostatin A. We now show that ZNF3 is mainly expressed in immature gametocytes and can here be detected in the cytoplasm and the nucleus. We have generated a glmS-based ZNF3 knockdown parasite line (ZNF3-KD) for phenotypic analyses. Cell-based assays revealed essential roles of ZNF3 in asexual blood stage replication, gametocyte maturation and exflagellation. BioID analyses identified mainly RNA-binding proteins as potential interaction partners of ZNF3 and several other interactors could be assigned to the translational repression complex of Plasmodium gametocytes. We have verified the binding of ZNF3 to selected putative interactors by protein-protein interaction assays. Our combined data suggest that ZNF3 is an RNA-binding protein with regulatory functions in transcript regulation crucial for male gametogenesis and hence human-to-mosquito transmission of P. falciparum.