Functions of mRNPs in RNA metabolism in Plasmodium falciparum

The emergence of resistance to frontline therapies in the malaria parasite underscores the pressing need for sustained drug discovery and development efforts. Protein translation is largely unexplored in malaria parasites, yet recent studies highlight the translation machinery as a promising target for novel antimalarial drugs. Our work on the DDX6-family RNA helicase DOZI has uncovered that the human malaria parasite Plasmodium falciparum utilizes different membrane-less cytoplasmic messenger ribonucleoprotein (mRNP) granules to control protein translation. These granules, akin to processing bodies, stress granules, and germ cell granules in model eukaryotes, orchestrate various mRNA metabolism functions, encompassing RNA decay, storage, and translation repression. Building upon these findings, we posit that distinct mRNP types play pivotal roles in global and transcript-specific mRNA regulation, governing parasite development, life stage transitions, and survival under stress. To elucidate these regulatory mechanisms, we employ cutting-edge techniques in reverse genetics, protein biochemistry, microscopy, transcriptomics, and proteomics. Our first objective is to identify molecular markers for distinct mRNPs, determine their protein and mRNA compositions, and characterize their dynamics across different parasite life stages and under stress conditions. Secondly, we will delve into the functions of key RNA-binding proteins within the mRNP granules, deciphering their roles in regulating mRNA stability, decay, and translatability. While these aims are sufficiently independent to be carried out in parallel, their intermediate results will mutually inform and reinforce one another, augmenting the overall significance and feasibility of the study. Collectively, the insights gained from these objectives will contribute to a comprehensive understanding of the diverse roles of mRNPs in regulating critical aspects of P. falciparum biology, laying the groundwork for discovering new antimalarial drugs. Project Number: 1R01AI187187-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: LIWANG CUI | Institution: UNIVERSITY OF SOUTH FLORIDA, TAMPA, FL | Award Amount: $375,000 | Activity Code: R01 | Study Section: Pathogenic Eukaryotes Study Section[PTHE] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01AI18718701A1