# RAPs-mediated post-transcriptional control in Apicomplexan parasites

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2022 · $560,570

## Abstract

Project Summary/Abstract
In the malaria parasite, gene regulation is heavily dependent on mechanisms acting at 
the post- transcriptional and translational levels. More importantly, Plasmodium possesses many 
atypical characteristics in both pathways when compared to its human host. These unusual 
features hence extend our therapeutic window against this deadly parasite, yet these 
characteristics have been poorly explored at the molecular level. The main goal of this project is 
to characterize the role of newly identified apicomplexan-specific RNA- binding proteins {RAPs) in 
parasite development and virulence, and to validate their potential as novel drug targets.
The fact that Plasmodium parasites modulate part of his gene expression at the post-transcriptional 
level was inspired by many early studies that demonstrated that the global proteomic profiles often 
lagged behind the transcriptional profiles. Our newly published large-scale bioinformatics 
reinforce this conjecture as we determined that at least 18% of all coding-gene are predicted 
to be potential RNA binding domain-containing protein (RBP). Furthermore, many of these parasite 
RBPs were experimentally shown to interact in situ with mRNAs. In all eukaryotic organisms, 
RBPs are essential to regulate mRNA processing at multiple levels including splicing, 
transport, mRNA stability and turnover, as well as mRNA localization and translational 
efficiency. In the human malaria parasite, very few RBPs have been characterized. We propose to 
address this knowledge gap by examining the function of the parasite specific RNA-binding 
 domain proteins abundant in Apicomplexans, or RAPs. More specifically, we will use 
state-of-the-art genomics, molecular, and cellular approaches to determine the role of the 21 
identified RAPs in parasite development and survival. In Aim 1, we will characterize the 
essentiality, subcellular localization and phenotypes of RAPs in P. falciparum across 
different developmental stage using novel CRISPR/Cas9 approaches. In Aim 2, we will define the 
global RAP- related ribonucleoprotein interaction network across various parasite 
developmental stages by developing high-throughput sequencing technologies and pull-down 
strategies followed by mass spectrometry analysis. Our complementary approaches will not only 
identify key specific RBPs contributing to parasite development, but also uncover unique 
post-transcriptional networks in a eukaryotic human pathogen. By providing 
fundamental insights into mechanisms regulating translation in Plasmodium, this project will 
improve our ability to design new drugs and novel lines of defense against malaria and many other 
infectious disease agents.

## Key facts

- **NIH application ID:** 10466864
- **Project number:** 5R01AI142743-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Karine Gaelle Le Roch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $560,570
- **Award type:** 5
- **Project period:** 2018-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466864

## Citation

> US National Institutes of Health, RePORTER application 10466864, RAPs-mediated post-transcriptional control in Apicomplexan parasites (5R01AI142743-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10466864. Licensed CC0.

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