Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum
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s41467-022-28981-7.pdf
Description
Published version
Size
2.7 MB
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Checksum (MD5)
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Author(s)
Hollin, Thomas
Abel, Steven
Falla, Alejandra
Pasaje, Charisse Flerida A
Bhatia, Anil
Hur, Manhoi
Kirkwood, Jay S
Saraf, Anita
Prudhomme, Jacques
De Souza, Amancio
Date Issued
2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Hollin, Thomas, Abel, Steven, Falla, Alejandra, Pasaje, Charisse Flerida A, Bhatia, Anil et al. 2022. "Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum." Nature Communications, 13 (1).
Version
Final published version
Abstract
AbstractThe 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-022-28981-7
