致死性最强的重症疟疾是由恶性疟原虫引起的。恶性疟原虫红细胞膜表面蛋白1是其红内期免疫识别的主要抗原之一，由var基因编码。疟原虫能利用var基因排斥性表达机制逃避免疫识别和清除。沉默var基因的激活是排斥性表达机制的重要环节。研究表明var反义长链非编码RNA(lncRNA)能特异性地激活var基因转录；同时，基因启动子区的组蛋白修饰也发生了明显变化。前期工作中，我们构建了恶性疟原虫lncRNA过表达系统并首次发现反义lncRNA仅依靠多态性的外显子序列即可激活var基因转录，然而目前已提出的var反义lncRNA激活机制无法解释该数据，说明lncRNA激活var基因的机制并未真正阐明。利用RNA-pulldown，我们筛选出反义lncRNA的结合蛋白Alba1。我们将以此为基础，探索var基因反义lncRNA协同Alba1及组蛋白修饰共同调节var基因激活的分子机制。

Plasmodium falciparum can cause lethal malaria. When P. falciparum parasitizes and reproduces in erythrocytes of infected individuals, it produces P. falciparum erythrocyte membrane protein 1, which is encoded by the var gene family. As one of the immunodominant antigens, the protein family allows parasite to escape from the host immune system by switching the var gene transcription. When var gene switches, a silent var gene is activated while the previously active var gene is repressed. It is demonstrated that the var gene could be activated by its antisense long non-coding RNA (aslncRNA), and the significant changes of the histone modifications were found on the promoter of the active var gene. In our previous study, we found that the polymorphic exonI sequence of var aslncRNA was competent to activate the var gene. However, the existing model cannot interpret these data. It means that the mechanism of aslncRNA-mediated var activation is still unclear. To further study the function of var aslncRNA, we have identified a var aslncRNA-binding protein, Alba1. Next, we will explore the molecular mechanism of var activation in association with Alba1 and histone modifications.