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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Jacqui, 2022. "Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28981-7
    DOI: 10.1038/s41467-022-28981-7
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    References listed on IDEAS

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    1. Suresh M. Ganesan & Alejandra Falla & Stephen J. Goldfless & Armiyaw S. Nasamu & Jacquin C. Niles, 2016. "Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    2. Stephen J. Goldfless & Jeffrey C. Wagner & Jacquin C. Niles, 2014. "Versatile control of Plasmodium falciparum gene expression with an inducible protein–RNA interaction," Nature Communications, Nature, vol. 5(1), pages 1-8, December.
    3. Doumet Georges Helou & Pedram Shafiei-Jahani & Richard Lo & Emily Howard & Benjamin P. Hurrell & Lauriane Galle-Treger & Jacob D. Painter & Gavin Lewis & Pejman Soroosh & Arlene H. Sharpe & Omid Akbar, 2020. "PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
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    Cited by:

    1. Thomas Hollin & Steven Abel & Charles Banks & Borislav Hristov & Jacques Prudhomme & Kianna Hales & Laurence Florens & William Stafford Noble & Karine G. Le Roch, 2024. "Proteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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