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A molecular switch in the efficiency of translation reinitiation controls expression of var2csa, a gene implicated in pregnancy-associated malaria.

TitleA molecular switch in the efficiency of translation reinitiation controls expression of var2csa, a gene implicated in pregnancy-associated malaria.
Publication TypeJournal Article
Year of Publication2013
AuthorsBancells C, Deitsch K
JournalMol Microbiol
Volume90
Issue3
Pagination472-88
Date Published2013 Nov
ISSN1365-2958
Abstract

Plasmodium falciparum malaria parasites export the protein PfEMP1 to the surface of infected erythrocytes, enabling them to adhere to receptors in the microvasculature and thereby avoid clearance by the spleen. The gene var2csa encodes the form of PfEMP1 that binds specifically within the placenta, causing pregnancy-associated malaria, and appears to not be expressed in the absence of a placenta. We previously described an upstream open reading frame (uORF) that is responsible for repression of translation of the downstream ORF (dORF) that encodes VAR2CSA, thus keeping the gene silent when parasites infect non-pregnant individuals. To elucidate the molecular mechanism by which this repression is overcome during pregnancy, we stably transformed parasites with reporter gene constructs designed to detect switches in the efficiency of dORF translation. We found that proper regulation of switching relies on two separate components, (i) active translation of the uORF and (ii) sequence-specific characteristics of the surrounding transcript, which together control the ability of the ribosome complex to reinitiate a second round of translation and thus express VAR2CSA. These results provide the first details of a molecular switch that allows parasites take advantage of the unique niche provided by the placenta.

DOI10.1111/mmi.12379
Alternate JournalMol. Microbiol.
PubMed ID23980802
PubMed Central IDPMC3938558
Grant ListR01 AI052390 / AI / NIAID NIH HHS / United States

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