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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.

SUBMITTER: Guizetti J

PROVIDER: S-EPMC5175341 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite.

Guizetti Julien J Guizetti Julien J Barcons-Simon Anna A Scherf Artur A

Nucleic acids research 20160727 20

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 ...[more]

PMID: 27466391

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Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite.

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Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite.

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