Pleiotropic Roles for the Plasmodium berghei RNA Binding Protein UIS12 in Transmission and Oocyst Maturation

Colonization of the mosquito host by Plasmodium parasites is achieved by sexually differentiated gametocytes. Gametocytogenesis, gamete formation and fertilization are tightly regulated processes, and translational repression is a major regulatory mechanism for stage conversion. Here, we present a characterization of a Plasmodium berghei RNA binding protein, UIS12, that contains two conserved eukaryotic RNA recognition motifs (RRM). Targeted gene deletion resulted in viable parasites that replicate normally during blood infection, but form fewer gametocytes. Upon transmission to Anopheles stephensi mosquitoes, both numbers and size of midgut-associated oocysts were reduced and their development stopped at an early time point. As a consequence, no salivary gland sporozoites were formed indicative of a complete life cycle arrest in the mosquito vector. Comparative transcript profiling in mutant and wild-type infected red blood cells revealed a decrease in transcript abundance of mRNAs coding for signature gamete-, ookinete-, and oocyst-specific proteins in uis12(-) parasites. Together, our findings indicate multiple roles for UIS12 in regulation of gene expression after blood infection in good agreement with the pleiotropic defects that terminate successful sporogony and onward transmission to a new vertebrate host.

Automated summary

The deletion of the UIS12 gene in Plasmodium parasites results in a decrease in gametocyte formation, oocyst development, and ultimately, the production of salivary gland sporozoites in Anopheles mosquitoes. Transcript profiling shows a reduction in specific protein coding mRNAs in mutant parasites, indicating the diverse regulatory roles of UIS12 in gene expression during blood infection.