Puf-Mediated Translation Control in Plasmodium

DESCRIPTION (provided by applicant): Protein translation is largely unexplored in the malaria parasites. A better understanding of this basic process of life may identify potential targets for developing new therapeutic interventions. Recent studies have revealed the essential roles of translation control during the life cycle of the malaria parasites, especially at the transition stages between the two hosts. The Plasmodium parasite genome encodes four members of Puf RNA-binding proteins, a family of transcript-specific translational regulators in eukaryotes. Puf proteins regulate development by binding to the 3' untranslated regions of the target mRNAs to control their translation. Our recent work shows that a Puf member in P. falciparum is a master regulator of protein translation and plays an important role in regulating sexual development. Based on these observations and different expression profiles of the Puf members in P. falciparum, we hypothesize that the Puf family translational repressors orchestrate parasite development and stage transitions by regulating translation of different sets of genes. To define the roles of Puf proteins in P. falciparum development, we propose to first characterize the functions of individual Puf genes during intraerythrocytic development and stage transitions by genetic knockout or knockdown and determine how the genetic manipulations affect parasite development. We will use complementary approaches to obtain a holistic view of the mRNAs associated with the Puf proteins and to identify pathways that are specifically targeted. The systematic approaches employed in this study will yield comprehensive information about functions of Puf proteins in regulating the developmental cycle of malaria parasites and provide novel insights into the evolution of Puf-mediated translation control in eukaryotes.