ArticleProceedings of the National Academy of Sciences of the United States of America2015
Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 154 citations in OpenAlex.
- The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections.PLoS pathogens · 2023Trial
- New insights on Plasmodium gene expression from direct RNA sequencing.Trends in parasitology · 2026Review
- Dynamic regulation of long non-coding RNAs across asexual and gametocyte development inbioRxiv : the preprint server for biology · 2026Article
- Mechanistic insights into coordinated var transcriptional switching in malaria parasites.The EMBO journal · 2026Article
- Genome-wide analysis of strand-specific transcription and DNA methylation inFrontiers in microbiology · 2026Article
- A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite.Nature communications · 2025Article
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
- Ectopic overexpression ofMicrobiology spectrum · 2025Article
- Insights into the evolution, virulence and speciation ofEmerging microbes & infections · 2024Article
- ThemSphere · 2024Article
- Transcriptomic analyses of differentially expressed human genes, micro RNAs and long-non-coding RNAs in severe, symptomatic and asymptomatic malaria infection.Scientific reports · 2024Article
- Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.International journal of molecular sciences · 2024Review
- Comparative analysis of peripheral whole blood transcriptome from asymptomatic carriers reveals upregulation of subsets of surface proteins implicated inBiochemistry and biophysics reports · 2024Article
- Proteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes.Nature communications · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites.Annual review of microbiology · 2023Review
- Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum.Nature communications · 2023Article
- Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023Review
- The role of long noncoding RNAs in malaria parasites.Trends in parasitology · 2023Review
- Discovery of RUF6 ncRNA-interacting proteins involved inLife science alliance · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The virulence of Plasmodium falciparum, the causative agent of the deadliest form of human malaria, is attributed to its ability to evade human immunity through antigenic variation. These parasites alternate between expression of variable antigens, encoded by members of a multicopy gene family named var. Immune evasion through antigenic variation depends on tight regulation of var gene expression, ensuring that only a single var gene is expressed at a time while the rest of the family is maintained transcriptionally silent. Understanding how a single gene is chosen for activation is critical for understanding mutually exclusive expression but remains a mystery. Here, we show that antisense long noncoding RNAs (lncRNAs) initiating from var introns are associated with the single active var gene at the time in the cell cycle when the single var upstream promoter is active. We demonstrate that these antisense transcripts are incorporated into chromatin, and that expression of these antisense lncRNAs in trans triggers activation of a silent var gene in a sequence- and dose-dependent manner. On the other hand, interference with these lncRNAs using complement peptide nucleic acid molecules down-regulated the active var gene, erased the epigenetic memory, and induced expression switching. Altogether, our data provide evidence that these antisense lncRNAs play a key role in regulating var gene activation and mutually exclusive expression.
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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.