Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, 171 77 Stockholm, Sweden.
Department of Cell and Molecular Biology, Uppsala University, Box-596, 751 24 Uppsala, Sweden.
Nat Microbiol. 2017 May 8;2:17068. doi: 10.1038/nmicrobiol.2017.68.
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.
妊娠相关疟疾通常涉及通过 PfEMP1-VAR2CSA 蛋白将感染疟原虫的红细胞与胎盘硫酸软骨素 A（CSA）结合。VAR2CSA 由上游开放阅读框翻译抑制。在这项研究中，我们报告 Pf 翻译增强因子（PTEF）可解除上游开放阅读框的抑制，从而促进 VAR2CSA 翻译。var2csa 转录寄生虫中的 VAR2CSA 蛋白水平依赖于 PTEF 的表达水平，并且需要 PfCalpain 对 PTEF 的蛋白水解处理来缓解上游开放阅读框的抑制。切割生成包含无活性-α-基序样结构域的 C 末端结构域。C 末端结构域允许细胞质穿梭，并与核糖体相互作用，促进 var2csa 编码序列的翻译去阻遏。它还可以增强异源翻译系统中的翻译，因此是在原生动物中发现的第一个非典型翻译增强因子。我们的结果表明 PTEF 参与调节感染红细胞与胎盘 CSA 的结合。
