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Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum

Thomas Hollin, Steven Abel, Alejandra Falla, Charisse Flerida A. Pasaje, Anil Bhatia, Manhoi Hur, Jay S. Kirkwood, Anita Saraf, Jacques Prudhomme, Amancio De Souza, Laurence Florens, Jacquin C. Niles and Karine G. Le Roch ()
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Thomas Hollin: University of California Riverside
Steven Abel: University of California Riverside
Alejandra Falla: Massachusetts Institute of Technology
Charisse Flerida A. Pasaje: Massachusetts Institute of Technology
Anil Bhatia: University of California
Manhoi Hur: University of California
Jay S. Kirkwood: University of California
Anita Saraf: Stowers Institute for Medical Research
Jacques Prudhomme: University of California Riverside
Amancio De Souza: University of California
Laurence Florens: Stowers Institute for Medical Research
Jacquin C. Niles: Massachusetts Institute of Technology
Karine G. Le Roch: University of California Riverside

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract The RAP (RNA-binding domain abundant in Apicomplexans) protein family has been identified in various organisms. Despite expansion of this protein family in apicomplexan parasites, their main biological functions remain unknown. In this study, we use inducible knockdown studies in the human malaria parasite, Plasmodium falciparum, to show that two RAP proteins, PF3D7_0105200 (PfRAP01) and PF3D7_1470600 (PfRAP21), are essential for parasite survival and localize to the mitochondrion. Using transcriptomics, metabolomics, and proteomics profiling experiments, we further demonstrate that these RAP proteins are involved in mitochondrial RNA metabolism. Using high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (eCLIP-seq), we validate that PfRAP01 and PfRAP21 are true RNA-binding proteins and interact specifically with mitochondrial rRNAs. Finally, mitochondrial enrichment experiments followed by deep sequencing of small RNAs demonstrate that PfRAP21 controls mitochondrial rRNA expression. Collectively, our results establish the role of these RAP proteins in mitoribosome activity and contribute to further understanding this protein family in malaria parasites.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28981-7

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DOI: 10.1038/s41467-022-28981-7

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