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Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor
Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Box 280,Nobels Vag 16, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Box 280,Nobels Vag 16, S-17177 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Box 280,Nobels Vag 16, S-17177 Stockholm, Sweden.;Natl Univ Singapore, Dept Microbiol, Singapore 117545, Singapore..
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2017 (English)In: NATURE MICROBIOLOGY, ISSN 2058-5276, Vol. 2, no 7, 17068Article in journal (Refereed) Published
Abstract [en]

Pregnancy-associated malaria commonly involves the binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate A (CSA) through the PfEMP1-VAR2CSA protein. VAR2CSA is translationally repressed by an upstream open reading frame. In this study, we report that the P. falciparum translation enhancing factor (PTEF) relieves upstream open reading frame repression and thereby facilitates VAR2CSA translation. VAR2CSA protein levels in var2csa-transcribing parasites are dependent on the expression level of PTEF, and the alleviation of upstream open reading frame repression requires the proteolytic processing of PTEF by PfCalpain. Cleavage generates a C-terminal domain that contains a sterile-alpha-motif-like domain. The C-terminal domain is permissive to cytoplasmic shuttling and interacts with ribosomes to facilitate translational derepression of the var2csa coding sequence. It also enhances translation in a heterologous translation system and thus represents the first non-canonical translation enhancing factor to be found in a protozoan. Our results implicate PTEF in regulating placental CSA binding of infected erythrocytes.

Place, publisher, year, edition, pages
2017. Vol. 2, no 7, 17068
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-333532DOI: 10.1038/nmicrobiol.2017.68ISI: 000406925300009PubMedID: 28481333OAI: oai:DiVA.org:uu-333532DiVA: diva2:1156948
Funder
Knut and Alice Wallenberg Foundation, KAW 2011.0081Swedish Research Council, VR/2012-2014/521-2011-3377 VR 2013-8778 2014-4423 2016-06264
Available from: 2017-11-14 Created: 2017-11-14 Last updated: 2017-11-14Bibliographically approved

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Mandava, Chandra SekharSanyal, Suparna

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