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A molecular switch in the efficiency of translation reinitiation controls expression of var2csa , a gene implicated in pregnancy‐associated malaria
Author(s) -
Bancells Cristina,
Deitsch Kirk W.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12379
Subject(s) - biology , open reading frame , psychological repression , translation (biology) , gene , genetics , placenta , computational biology , microbiology and biotechnology , gene expression , messenger rna , pregnancy , peptide sequence , fetus
Summary P lasmodium 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 VAR 2 CSA , 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 VAR 2 CSA . These results provide the first details of a molecular switch that allows parasites take advantage of the unique niche provided by the placenta.