ArticlePLoS pathogens2009
An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 110 citations in OpenAlex.
- Epigenetics and chromatin structure regulateeLife · 2026Article
- Mechanistic insights into coordinated var transcriptional switching in malaria parasites.The EMBO journal · 2026Article
- Epigenetics and chromatin structure regulatebioRxiv : the preprint server for biology · 2026Article
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
- Transcription and Copy Number Variation of Plasmodium falciparum var2csa among Nonpregnant Malaria Patients in Thailand.The American journal of tropical medicine and hygiene · 2025Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- The human malaria parasiteProceedings of the National Academy of Sciences of the United States of America · 2023Article
- A coordinated transcriptional switching network mediates antigenic variation of human malaria parasites.eLife · 2022Article
- A nuclear redox sensor modulates gene activation andProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.Nucleic acids research · 2022Article
- Functional characterization of 5' UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans.Malaria journal · 2022Article
- The RNA structurome in the asexual blood stages of malaria pathogenRNA biology · 2021Article
- The role of upstream open reading frames in translation regulation in the apicomplexan parasitesParasitology · 2021Review
- Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites.BMC ecology and evolution · 2021Article
- Histone modifications associated with gene expression and genome accessibility are dynamically enriched at Plasmodium falciparum regulatory sequences.Epigenetics & chromatin · 2020Article
- Article
- High-Resolution Mapping of Transcription Initiation in the Asexual Stages ofFrontiers in cellular and infection microbiology · 2020Article
- Protein-RNA interactions important for Plasmodium transmission.PLoS pathogens · 2019Review
- Neutrophil extracellular traps drive inflammatory pathogenesis in malaria.Science immunology · 2019Article
- Independent regulation of Plasmodium falciparum rif gene promoters.Scientific reports · 2018Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.