Related Experiment Video
Updated: Jun 1, 2026
10:22
Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
Published on: December 4, 2015
Two Plasmodium vivax hypnozoite-expressed RNA-binding proteins inhibit liver stage replication.
Kim Chi Vo1,2, Riëtte van Biljon3, Gigliola Zanghi4
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. kvo@som.umaryland.edu.
Nature Communications
|May 30, 2026
Summary
Plasmodium vivax malaria relapses are caused by dormant liver stages called hypnozoites. Researchers identified two proteins, IESI-1 and IESI-2, that inhibit liver stage development, revealing a potential mechanism for hypnozoite formation.
Area of Science:
- Molecular Parasitology
- Malaria Pathogenesis
- RNA Biology
Background:
- Plasmodium vivax causes malaria relapses through dormant liver-stage hypnozoites.
- The molecular mechanisms maintaining hypnozoite quiescence are largely unknown.
- Hypnozoites are hypothesized to actively suppress liver-stage development (schizogony).
Purpose of the Study:
- To identify molecular factors involved in maintaining the hypnozoite quiescent state.
- To investigate the functional role of novel RNA-binding proteins in Plasmodium liver stages.
Main Methods:
- Differential transcriptome analysis of Plasmodium vivax hypnozoites.
- Expression of candidate RNA-binding proteins in Plasmodium yoelii liver stages.
- Assessment of liver stage schizogony inhibition.
- RNA interactome screening to identify bound RNA motifs.
Main Results:
- Two hypnozoite-expressed transcripts encoding putative RNA-binding proteins were identified.
- Individual expression of these proteins (IESI-1 and IESI-2) in P. yoelii liver stages blocked schizogony.
- Parasites expressing IESI-1 or IESI-2 remained small and uninucleate, indicating suppressed development.
- Specific RNA motifs were enriched in interactomes, suggesting targeted RNA binding.
Conclusions:
- IESI-1 and IESI-2 are key inhibitors of Plasmodium liver stage schizogony.
- These proteins represent a potential molecular mechanism underlying hypnozoite formation and dormancy.
- Findings provide functional evidence for active suppression of development in malaria hypnozoites.
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