AUTHOR=Kumar Sudhir , Abatiyow Biley A. , Haile Meseret T. , Oualim Kenza M. Z. , Leeb Amanda S. , Vaughan Ashley M. , Kappe Stefan H.I. 

TITLE=A Putative Plasmodium RNA-Binding Protein Plays a Critical Role in Female Gamete Fertility and Parasite Transmission to the Mosquito Vector

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.825247

DOI=10.3389/fcell.2022.825247

ISSN=2296-634X

ABSTRACT=<p><italic>Plasmodium falciparum</italic> sexual stage gametocytes are critical for parasite transmission from the human host to the mosquito vector. Mature gametocytes generate fertile male (micro-) or female (macro-) gametes upon activation inside the mosquito midgut. While a number of parasite genes have been described that are critical for <italic>P. falciparum</italic> gametogenesis and fertility, no parasite gene has been shown to have a unique function in macrogametes. The genome of <italic>P. falciparum</italic> encodes numerous RNA-binding proteins. We identified a novel protein containing a putative RNA-binding domain, which we named Macrogamete-Contributed Factor Essential for Transmission (MaCFET). This protein is expressed in the asexual and sexual stages. Parasites that carry a deletion of <italic>MaCFET</italic> (<italic>Pfmacfet¯</italic>), developed normally as asexual stages, indicating that its function is not essential for the asexual proliferation of the parasite <italic>in vitro</italic>. Furthermore, <italic>Pfmacfet¯</italic> male and female gametocytes developed normally and underwent activation to form microgametes and macrogametes. However, by utilizing genetic crosses, we demonstrate that <italic>Pfmacfet¯</italic> parasites suffer a complete female-specific defect in successful fertilization. Therefore, <italic>Pf</italic>MaCFET is a critical female-contributed factor for parasite transmission to the mosquito. Based on its putative RNA-binding properties, <italic>Pf</italic>MaCFET might be in involved in the regulation of mRNAs that encode female-specific functions for fertilization or female-contributed factors needed post fertilization.</p>