1. Regulation of PfEMP1–VAR2CSA translation by a Plasmodium translation-enhancing factor
- Author
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Sonia Barbieri, Suparna Sanyal, Mehdi Ghorbal, Chandra Sekhar Mandava, Nicolas Joannin, Maria del Pilar Quintana, Jose-Juan Lopez-Rubio, Alejandra Frasch, Antonio Lanzavecchia, Mats Wahlgren, Oscar Franzén, Sherwin Chan, Jun-Hong Ch’ng, Mattias Vesterlund, Department of Microbiology Tumor and Cell Biology [Stockholm], Karolinska Institutet [Stockholm], Uppsala University, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Icahn School of Medicine at Mount Sinai [New York] (MSSM), and Scuola Universitaria Professionale della Svizzera italiana
- Subjects
0301 basic medicine ,Plasmodium ,Erythrocytes ,Placenta ,Protozoan Proteins ,Applied Microbiology and Biotechnology ,Ribosome ,falciparum ,Pregnancy ,Protein biosynthesis ,Malaria, Falciparum ,Derepression ,ComputingMilieux_MISCELLANEOUS ,Regulation of gene expression ,Gene expression regulation ,Chemistry ,Calpain ,Chondroitin Sulfates ,Translation (biology) ,Open reading frame ,Open reading frames ,3. Good health ,Cell biology ,Erythrocyte ,embryonic structures ,Female ,Human ,Microbiology (medical) ,Protozoan proteins ,Chondroitin sulfate ,plasmodium falciparum ,Immunology ,Plasmodium falciparum ,Antigens, Protozoan ,Protozoal protein ,Protein degradation ,Microbiology ,03 medical and health sciences ,Open Reading Frames ,Var2csa protein ,Pregnancy complication ,Upstream open reading frame ,parasitic diseases ,Genetics ,Humans ,Parasite antigen ,Antigens ,Psychological repression ,Chondroitin sulfates ,Malaria falciparum ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,protozoan ,parasitic ,Cell Biology ,Malaria ,030104 developmental biology ,Metabolism ,Gene Expression Regulation ,Pregnancy complications ,Pregnancy Complications, Parasitic ,Protein Biosynthesis ,Proteolysis ,Parasitology ,Protein synthesis - Abstract
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. © 2017 Macmillan Publishers Limited. All rights reserved.
- Published
- 2017
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