Macedo-Silva Tatiane, Araujo Rosana Beatriz Duque, Meissner Kamila Anna, Fotoran Wesley Luzetti, Medeiros Márcia Melo, de Azevedo Mauro Ferreira, Wunderlich Gerhard
Department of Parasitology, Institute for Biomedical Sciences, University of São Paulo, Avenida Professor Lineu Prestes, 1374, São Paulo, Brazil.
PLoS One. 2017 Aug 11;12(8):e0183129. doi: 10.1371/journal.pone.0183129. eCollection 2017.
The genome of the malaria parasite Plasmodium falciparum contains the surf gene family which encodes large transmembrane proteins of unknown function. While some surf alleles appear to be expressed in sexual stages, others occur in asexual blood stage forms and may be associated to virulence-associated processes and undergo transcriptional switching. We accessed the transcription of surf genes along multiple invasions by real time PCR. Based on the observation of persistent expression of gene surf4.1, we created a parasite line which expresses a conditionally destabilized SURFIN4.1 protein. Upon destabilization of the protein, no interference of parasite growth or morphological changes were detected. However, we observed a strong increase in the transcript quantities of surf4.1 and sometimes of other surf genes in knocked-down parasites. While this effect was reversible when SURFIN4.1 was stabilized again after a few days of destabilization, longer destabilization periods resulted in a transcriptional switch away from surf4.1. When we tested if a longer transcript half-life was responsible for increased transcript detection in SURFIN4.1 knocked-down parasites, no alteration was found compared to control parasite lines. This suggests a specific feedback of the expressed SURFIN protein to its transcript pointing to a novel type of regulation, inedited in Plasmodium.
恶性疟原虫的基因组包含surf基因家族，该家族编码功能未知的大型跨膜蛋白。虽然一些surf等位基因似乎在有性阶段表达，但其他等位基因出现在无性血液阶段形式中，可能与毒力相关过程有关，并经历转录转换。我们通过实时PCR检测了多次入侵过程中surf基因的转录情况。基于对surf4.1基因持续表达的观察，我们构建了一个表达条件性不稳定的SURFIN4.1蛋白的寄生虫株。在该蛋白不稳定后，未检测到对寄生虫生长的干扰或形态变化。然而，我们观察到在敲低的寄生虫中，surf4.1以及有时其他surf基因的转录本数量大幅增加。当在不稳定几天后再次使SURFIN4.1稳定时，这种效应是可逆的，但更长时间的不稳定期会导致转录从surf4.1转换。当我们测试较长的转录本半衰期是否导致在敲低SURFIN4.1的寄生虫中检测到的转录本增加时，与对照寄生虫株相比未发现变化。这表明表达的SURFIN蛋白对其转录本有特定的反馈，指向一种在疟原虫中未编辑过的新型调控方式。
