title: Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite.
abstract: Monoallelic expression of the var multigene family enables immune evasion of the malaria parasite Plasmodium falciparum in its human host. At a given time only a single member of the 60-member var gene family is expressed at a discrete perinuclear region called the 'var expression site'. However, the mechanism of var gene counting remains ill-defined. We hypothesize that activation factors associating specifically with the expression site play a key role in this process. Here, we investigate the role of a GC-rich non-coding RNA (ncRNA) gene family composed of 15 highly homologous members. GC-rich genes are positioned adjacent to var genes in chromosome-central gene clusters but are absent near subtelomeric var genes. Fluorescence in situ hybridization demonstrates that GC-rich ncRNA localizes to the perinuclear expression site of central and subtelomeric var genes in trans. Importantly, overexpression of distinct GC-rich ncRNA members disrupts the gene counting process at the single cell level and results in activation of a specific subset of var genes in distinct clones. We identify the first trans-acting factor targeted to the elusive perinuclear var expression site and open up new avenues to investigate ncRNA function in antigenic variation of malaria and other protozoan pathogens.
authors.affiliation: Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, 75724, France julien.guizetti@pasteur.fr.|INSERM U1201, F-75724 Paris, France.|CNRS ERL9195, F-75724 Paris, France.
authors.forename: Julien
authors.identifier: http://orcid.org/0000-0002-7735-4689
authors.initials: J
authors.lastname: Guizetti
authors.affiliation: Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, 75724, France.|INSERM U1201, F-75724 Paris, France.|CNRS ERL9195, F-75724 Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Barcons-Simon
authors.affiliation: Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, 75724, France artur.scherf@pasteur.fr.|INSERM U1201, F-75724 Paris, France.|CNRS ERL9195, F-75724 Paris, France.
authors.forename: Artur
authors.initials: A
authors.lastname: Scherf
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016778:Malaria, Falciparum / Q000469:parasitology*; D008856:Microscopy, Fluorescence; D009690:Nucleic Acid Conformation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics*; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D015800:Protozoan Proteins; D022661:RNA, Untranslated; C085731:erythrocyte membrane protein 1, Plasmodium falciparum