title: Nuclear pores and perinuclear expression sites of var and ribosomal DNA genes correspond to physically distinct regions in Plasmodium falciparum.
abstract: The human malaria parasite Plasmodium falciparum modifies the erythrocyte it infects by exporting variant proteins to the host cell surface. The var gene family that codes for a large, variant adhesive surface protein called P. falciparum erythrocyte membrane protein 1 (PfEMP1) plays a particular role in this process, which is linked to pathogenesis and immune evasion. A single member of this gene family is highly transcribed while the other 59 members remain silenced. Importantly, var gene transcription occurs at a spatially restricted, but yet undefined, perinuclear site that is distinct from repressed var gene clusters. To advance our understanding of monoallelic expression, we investigated whether nuclear pores associate with the var gene expression site. To this end, we studied the nuclear pore organization during the asexual blood stage using a specific antibody directed against a subunit of the nuclear pore, P. falciparum Nup116 (PfNup116). Ring and schizont stage parasites showed highly polarized nuclear pore foci, whereas in trophozoite stage nuclear pores redistributed over the entire nuclear surface. Colocalization studies of var transcripts and anti-PfNup116 antibodies showed clear dissociation between nuclear pores and the var gene expression site in ring stage. Similar results were obtained for another differentially transcribed perinuclear gene family, the ribosomal DNA units. Furthermore, we show that in the poised state, the var gene locus is not physically linked to nuclear pores. Our results indicate that P. falciparum does form compartments of high transcriptional activity at the nuclear periphery which are, unlike the case in yeast, devoid of nuclear pores.
authors.affiliation: Département de Parasitologie et Mycologie, Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Guizetti
authors.forename: Rafael Miyazawa
authors.initials: RM
authors.lastname: Martins
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Guadagnini
authors.forename: Aurélie
authors.initials: A
authors.lastname: Claes
authors.forename: Artur
authors.initials: A
authors.lastname: Scherf
mesh_terms: D002478:Cells, Cultured; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D015870:Gene Expression; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006801:Humans; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D053058:Trophozoites / Q000000981:diagnostic imaging / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D004275:DNA, Ribosomal; D028861:Nuclear Pore Complex Proteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum