An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.

Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected eryt...

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Autores principales:	Borko Amulic, Ali Salanti, Thomas Lavstsen, Morten A Nielsen, Kirk W Deitsch
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/192eb877348e42c9bb4ccfdb84c1d976
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spelling	oai:doaj.org-article:192eb877348e42c9bb4ccfdb84c1d9762021-11-25T05:47:22ZAn upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.1553-73661553-737410.1371/journal.ppat.1000256https://doaj.org/article/192eb877348e42c9bb4ccfdb84c1d9762009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19119419/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue.Borko AmulicAli SalantiThomas LavstsenMorten A NielsenKirk W DeitschPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 1, p e1000256 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Borko Amulic Ali Salanti Thomas Lavstsen Morten A Nielsen Kirk W Deitsch An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
description	Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of the world. Pregnant women are exceptionally vulnerable to severe consequences of the infection, due to the specific adhesion of parasite-infected erythrocytes in the placenta. This adhesion is mediated by a unique variant of PfEMP1, a parasite encoded, hyper-variable antigen placed on the surface of infected cells. This variant, called VAR2CSA, binds to chondroitin sulfate A on syncytiotrophoblasts in the intervillous space of placentas. VAR2CSA appears to only be expressed in the presence of a placenta, suggesting that its expression is actively repressed in men, children or non-pregnant women; however, the mechanism of repression is not understood. Using cultured parasite lines and reporter gene constructs, we show that the gene encoding VAR2CSA contains a small upstream open reading frame that acts to repress translation of the resulting mRNA, revealing a novel form of gene regulation in malaria parasites. The mechanism underlying this translational repression is reversible, allowing high levels of protein translation upon selection, thus potentially enabling parasites to upregulate expression of this variant antigen in the presence of the appropriate host tissue.
format	article
author	Borko Amulic Ali Salanti Thomas Lavstsen Morten A Nielsen Kirk W Deitsch
author_facet	Borko Amulic Ali Salanti Thomas Lavstsen Morten A Nielsen Kirk W Deitsch
author_sort	Borko Amulic
title	An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
title_short	An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
title_full	An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
title_fullStr	An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
title_full_unstemmed	An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
title_sort	upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/192eb877348e42c9bb4ccfdb84c1d976
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An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria.

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