Jing Qingqing, Cao Long, Zhang Liangliang, Cheng Xiu, Gilbert Nicolas, Dai Xueyu, Sun Maoxin, Liang Shaohui, Jiang Lubin
Unit of Human Parasite Molecular and Cell Biology, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Microbiol. 2018 Dec 18;9:3117. doi: 10.3389/fmicb.2018.03117. eCollection 2018.
erythrocyte membrane protein 1, encoded by gene, is an immunodominant antigen mediating immune evasion in humans. At a given time, only a single gene is commonly expressed in one parasite. However, the regulation mechanism of transcription remains largely unknown. In this study, we identified the antisense long non-coding RNA (aslncRNA) derived from intron as an activation factor for the corresponding gene. The exogenous artificial aslncRNA transcribed by T7 RNA polymerase from episome can specifically activate the homologous gene, and the exogenous aslncRNA activates transcription of both mRNA and endogenous aslncRNA in a manner independent of the conserved intron sequence within the gene family. Interestingly, the newly activated gene and the previously dominant gene then could be co-expressed in the same parasite nuclei, which suggests that the aslncRNA-mediated gene activation could escape from the control of mutually exclusively expression of the gene family. Together, our work shows that aslncRNA is the activator responsible for gene transcriptional regulation.
由该基因编码的红细胞膜蛋白1是介导人类免疫逃逸的免疫显性抗原。在特定时间,一种寄生虫中通常仅单个该基因表达。然而,该基因转录的调控机制仍 largely未知。在本研究中,我们鉴定出源自该基因内含子的反义长链非编码RNA(aslncRNA)作为相应该基因的激活因子。由T7 RNA聚合酶从附加体转录的外源性人工该aslncRNA可特异性激活同源该基因,并且外源性aslncRNA以独立于该基因家族内保守内含子序列的方式激活该mRNA和内源性aslncRNA的转录。有趣的是,新激活的该基因和先前占主导地位的该基因随后可在同一寄生虫细胞核中共表达,这表明aslncRNA介导的该基因激活可逃避该基因家族相互排斥性表达的控制。总之,我们的工作表明该aslncRNA是负责该基因转录调控的激活因子。