Swearingen, K. | bioRxiv Science

bioRxiv2026

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

Sexual maturation and fertility of the malaria causing parasite, Plasmodium spp., is 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 characterized the role of the CCCH-type zinc-finger protein Plasmodium falciparum Male Development 3 (PfMD3) in the formation of gametes. Genetic disruption of PfMD3 revealed a male fertility defect that decreased infectivity to mosquitoes. Molecular characterization of PfMD3 revealed its binding to mRNA transcripts associated with male gamete development through a specific RNA sequence. Gametocyte proteins encoded by these PfMD3-bound transcripts decreased significantly in PfMD3 knockout parasites, suggesting that PfMD3 impacts translation. In addition to RNA-binding, PfMD3 also interacts with proteins involved in mRNA processing and nuclear export that influence translational regulation. This study establishes PfMD3 as an RNA-binding protein that impacts lineage-specific translation and male gamete fertility.

molecular biology↗

bioRxiv2017

Integrated transcriptomic, proteomic and epigenomic analysis of Plasmodium vivax salivary-gland sporozoites

Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper-cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoites is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, we undertook a comprehensive transcriptomic and histone epigenetic characterization of P. vivax sporozoites. The salivary-gland sporozoite transcriptome is heavily composed of transcripts associated with functions needed for early infection of the vertebrate host and development within hepatocytes. Through comparisons to recently published proteome data for the P. vivax sporozoite, our study finds that although highly transcribed, these transcripts are not detectable as proteins and may be regulated through translational repression; a finding we test for a small subset of transcripts and proteins through immunofluorescent microscopy of sporozoites and liver stages in humanized mice. We identify differential transcription between the sporozoite and published transcriptomes of asexual blood-stages and mixed versus hypnozoite-enriched liver stages. These comparisons point to multiple layers of transcriptional, post-transcriptional and post-translational control that appear active in sporozoites and to a lesser extent hypnozoites, but largely absent in replicating liver schizonts or mixed blood-stages. Common transcripts up-regulated in sporozoites and hypnozoites compared to mixed (i.e., schizont) liver-stages identify genes linked to dormancy/persistence in bacteria, amoebae and plants. We also characterise histone epigenetic modifications in the P. vivax sporozoite and explore their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite as a tightly programmed stage primed to infect the human host and identifies potential mechanisms for hypnozoite-formation that may be further explored in liver stage models.

microbiology↗