The CCCH-type zinc-finger PfMD3 promotes translation for malaria parasite transmission

Abstract Sexual maturation and fertility of the malaria-causing parasite, Plasmodium spp., are critical to transmission between hosts. This developmental process involves an intricate gene expression regulatory network that drives gametocyte commitment, development, and the production of male and female gametes. Here, we characterize the role of the CCCH-type zinc-finger protein Plasmodium falciparum Male Development 3 ( Pf MD3) in the formation of gametes. Genetic disruption of Pf MD3 reveals a male fertility defect that decreases infectivity to mosquitoes. Molecular characterization of Pf MD3 reveals its binding to mRNA transcripts is associated with male gamete development through a specific RNA sequence. Gametocyte proteins encoded by these Pf MD3-bound transcripts decrease significantly in Pf MD3 knockout parasites, suggesting that Pf MD3 impacts translation. In addition to RNA-binding, Pf MD3 also interacts with proteins involved in mRNA processing and nuclear export that influence translational regulation. This study establishes Pf MD3 as an RNA-binding protein that impacts lineage-specific translation and male gamete fertility.