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Plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. RNA binding proteins (RBPs) provide one mechanism for modulation of RNA function. To explore the role ofPlasmodium RBPs during parasite replication, we searched for RBPs that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. We identified a parasite ortholog of theMei2 (Me iosisi nhibited 2) RBP that is conserved amongPlasmodium species (PlasMei2) and exclusively transcribed in liver stage parasites. Epitope-taggedPlasmodium yoelii PlasMei2 was expressed only during liver stage schizogony and showed an apparent granular cytoplasmic location. Knockout ofPlasMei2 (plasmei2 − ) inP. yoelii only affected late liver stage development. TheP. yoelii plasmei2 − liver stage size increased progressively until late in development, similar to wild-type parasite development. However,P. yoelii plasmei2 − liver stage schizonts exhibited an abnormal DNA segregation phenotype and failed to form exoerythrocytic merozoites. Consequently the cellular integrity ofP. yoelii plasmei2 − liver stages became increasingly compromised late in development and the majority ofP. yoelii plasmei2 − underwent cell death by the time wild-type liver stages mature and release merozoites. This resulted in a complete block ofP. yoelii plasmei2 − transition from liver stage to blood stage infection in mice. Our results show for the first time the importance of aPlasmodium RBP in the coordinated progression of late liver stage schizogony and maturation of new invasive forms.

A Plasmodium yoelii Mei2-Like RNA Binding Protein Is Essential for Completion of Liver Stage Schizogony