Plasmodium falciparum var Gene Is Activated by Its Antisense Long Noncoding RNA
Plasmodium falciparum var Gene Is Activated by Its Antisense Long Noncoding RNA
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恶性疟原虫变种基因被其反义长非编码RNA激活
DOI：
10.3389/fmicb.2018.03117
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发表时间：
2018-12-18
影响因子：
5.2
通讯作者：
Jiang, Lubin
中科院分区：
文献类型：
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作者：
Jing, Qingqing;Cao, Long;Jiang, Lubin
恶性疟原虫红细胞膜蛋白1是由var基因编码的一种免疫显性抗原，可介导人体的免疫逃避。在给定的时间，只有一个var基因通常在一种寄生虫中表达。然而，var转录的调控机制在很大程度上仍然未知。在这项研究中，我们确定了反义长非编码RNA（aslncRNA）来自var内含子作为相应的var基因的激活因子。T7 RNA聚合酶从附加体转录的外源性人工var aslncRNA可以特异性激活同源var基因，并且外源性aslncRNA以不依赖于var基因家族内保守内含子序列的方式激活var mRNA和内源性aslncRNA的转录。有趣的是，新激活的var基因和先前显性的var基因可以在相同的寄生虫核中共表达，这表明aslncRNA介导的var基因激活可以逃脱var基因家族的互斥表达的控制。总之，我们的工作表明var aslncRNA是负责var基因转录调控的激活剂。
Plasmodium falciparum erythrocyte membrane protein 1, encoded by var gene, is an immunodominant antigen mediating immune evasion in humans. At a given time, only a single var gene is commonly expressed in one parasite. However, the regulation mechanism of var transcription remains largely unknown. In this study, we identified the antisense long non-coding RNA (aslncRNA) derived from var intron as an activation factor for the corresponding var gene. The exogenous artificial var aslncRNA transcribed by T7 RNA polymerase from episome can specifically activate the homologous var gene, and the exogenous aslncRNA activates transcription of both var mRNA and endogenous aslncRNA in a manner independent of the conserved intron sequence within the var gene family. Interestingly, the newly activated var gene and the previously dominant var gene then could be co-expressed in the same parasite nuclei, which suggests that the aslncRNA-mediated var gene activation could escape from the control of mutually exclusively expression of the var gene family. Together, our work shows that var aslncRNA is the activator responsible for var gene transcriptional regulation.