ArticleNature2014
Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 89 citations in OpenAlex.
- A critical role of the histone lysine demethylase JmjC1 in regulating severe malaria-associated virulence genes in Plasmodium falciparum.Nature communications · 2026Article
- Specialized RNA decay fine-tunes monogenic antigen expression in Trypanosoma brucei.Nature microbiology · 2026Article
- m5C methylation of mitochondrial RNA and non-coding RNA by NSUN3 is associated with variant gene expression and asexual blood-stage development in Plasmodium falciparum.Parasites & vectors · 2025Article
- RNA polymerase III is involved in regulatingeLife · 2024Article
- Size-dependent enhancement of gene expression by Plasmodium 5'UTR introns.Parasites & vectors · 2024Article
- Extracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum.Nature communications · 2023Article
- The role of long noncoding RNAs in malaria parasites.Trends in parasitology · 2023Review
- Erythrocyte miRNA-92a-3p interactions with PfEMP1 as determinants of clinical malaria.Functional & integrative genomics · 2023Article
- Discovery of RUF6 ncRNA-interacting proteins involved inLife science alliance · 2023Article
- Emerging biology of noncoding RNAs in malaria parasites.PLoS pathogens · 2022Review
- A single point mutation in the Plasmodium falciparum 3'-5' exonuclease does not alter piperaquine susceptibility.Malaria journal · 2022Article
- Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.Nucleic acids research · 2022Article
- Resetting var Gene Transcription in Plasmodium falciparum.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The RNA structurome in the asexual blood stages of malaria pathogenRNA biology · 2021Article
- A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum.Nucleic acids research · 2021Article
- Article
- PfAP2-EXP2, an Essential Transcription Factor for the Intraerythrocytic Development ofFrontiers in cell and developmental biology · 2021Article
- Isolation of Mutants With Reduced Susceptibility to Piperaquine From a Mutator of the Rodent Malaria ParasiteFrontiers in cellular and infection microbiology · 2021Article
- Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum.Parasites & vectors · 2020Article
- Article
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase II and upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.
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