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RAP proteins regulate apicoplast noncoding RNA processing in Plasmodium falciparum.

Thomas Hollin1, Zeinab Chahine1, Steven Abel1

  • 1Department of Molecular, Cell and Systems Biology, University of California, Riverside, Riverside, CA, USA.

Cell Reports
|June 27, 2025
PubMed
Summary
This summary is machine-generated.

Two essential RNA-binding proteins, PfRAP03 and PfRAP08, control gene expression within the malaria parasite's apicoplast. Their depletion impacts parasite survival, highlighting new drug targets for malaria treatment.

Keywords:
CP: MicrobiologyPlasmodiumRAP proteinRNA bindingapicoplastmalariapost-transcriptional regulation

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Area of Science:

  • Molecular biology
  • Parasitology
  • Genetics

Background:

  • The malaria parasite Plasmodium falciparum possesses an essential, non-photosynthetic apicoplast.
  • The apicoplast is a key organelle and a potential drug target due to its unique biology.

Purpose of the Study:

  • To characterize the function and targets of PfRAP03 and PfRAP08, members of the RNA-binding domain abundant in apicomplexans (RAP) protein family.
  • To validate the essentiality and apicoplast localization of these RAP proteins in P. falciparum.

Main Methods:

  • Generation of inducible knockdown lines in P. falciparum.
  • Transcriptomic analysis to assess gene expression changes upon protein depletion.
  • Enhanced crosslinking immunoprecipitation sequencing (eCLIP-seq) to identify RNA targets.

Main Results:

  • PfRAP03 and PfRAP08 are essential for P. falciparum survival and localize to the apicoplast.
  • Depletion of PfRAP03 and PfRAP08 significantly alters apicoplast gene expression.
  • PfRAP03 targets apicoplast ribosomal RNAs, while PfRAP08 targets transfer RNAs.

Conclusions:

  • PfRAP proteins play a crucial role in regulating apicoplast gene expression in P. falciparum.
  • These findings reveal parasite-specific organellar pathways with potential biomedical significance for antimalarial drug development.