An Upstream Open Reading Frame Controls Translation of var2csa, a Gene Implicated in Placental Malaria

PLoS Pathogens

Ali Salanti¹  Thomas Lavstsen¹  Morten A. Nielsen¹  Borko Amulic²  Kirk W. Deitsch² 

[1] Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen, Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America

关键词: Parasitic diseases;    Malarial parasites;    Protein translation;    Gene expression;    Luciferase;    Messenger RNA;    Gene prediction;    Plasmodium;   

DOI  :  10.1371/journal.ppat.1000256

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY