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Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor.
Journal article

Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor.

  • Chan S Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
  • Frasch A Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
  • Mandava CS Department of Cell and Molecular Biology, Uppsala University, Box-596, 751 24 Uppsala, Sweden.
  • Ch'ng JH Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
  • Quintana MDP Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
  • Vesterlund M Cancer Proteomics, Department of Oncology-Pathology, Karolinska Institutet, 17176 Stockholm, Sweden.
  • Ghorbal M University of Montpellier, Faculty of Medicine, Laboratory of Parasitology-Mycology, Montpellier F34090, France.
  • Joannin N Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
  • Franzén O Department of Genetics and Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Lopez-Rubio JJ University of Montpellier, Faculty of Medicine, Laboratory of Parasitology-Mycology, Montpellier F34090, France.
  • Barbieri S Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland.
  • Lanzavecchia A Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland.
  • Sanyal S Department of Cell and Molecular Biology, Uppsala University, Box-596, 751 24 Uppsala, Sweden.
  • Wahlgren M Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
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  • 2017-05-09
Published in:
  • Nature microbiology. - 2017
Antigens, Protozoan
Calpain
Chondroitin Sulfates
Erythrocytes
Female
Gene Expression Regulation
Humans
Malaria, Falciparum
Open Reading Frames
Placenta
Plasmodium
Plasmodium falciparum
Pregnancy
Pregnancy Complications, Parasitic
Protein Biosynthesis
Proteolysis
Protozoan Proteins
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/39669
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