NEAT1 modulates herpes simplex virus-1 replication by regulating viral gene transcription.
NEAT1 modulates herpes simplex virus-1 replication by regulating viral gene transcription.
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NEAT1 通过调节病毒基因转录来调节单纯疱疹病毒 1 复制
DOI：
10.1007/s00018-016-2398-4
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发表时间：
2017-03
期刊：
影响因子：
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通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Wang Z;Fan P;Zhao Y;Zhang S;Lu J;Xie W;Jiang Y;Lei F;Xu N;Zhang Y
核旁斑组装转录本1(NEAT1)是核团的重要结构平台，是核团的一种。作为一种应激诱导的lncRNA，NEAT1在病毒感染后表达增加，但对其在单纯疱疹病毒1型(HSV-1)复制中的作用却知之甚少。在这里，我们证明了HSV-1感染以STAT3依赖的方式增加了NEAT1的表达和副斑点的形成。NEAT1等副斑点蛋白组分P54nrb和PSPC1可与HSV-1基因组DNA结合。PSPC1通过与STAT3结合，促进STAT3与病毒基因启动子之间的相互作用，促进病毒基因表达和病毒复制。此外，含有NEAT1 siRNA或STAT3 siRNA的温敏凝胶有效地修复了HSV-1感染引起的小鼠皮肤损伤。我们的结果为深入了解lncRNAs在病毒基因的表观遗传控制中的作用和副蛋白的功能提供了洞察力。
Nuclear paraspeckle assembly transcript 1 (NEAT1) is the crucial structural platform of paraspeckles, which is one type of nuclear bodies. As a stress-induced lncRNA, the expression of NEAT1 increases in response to viral infection, but little is known about the role of NEAT1 or paraspeckles in the replication of herpes simplex virus-1 (HSV-1). Here, we demonstrate that HSV-1 infection increases NEAT1 expression and paraspeckle formation in a STAT3-dependent manner. NEAT1 and other paraspeckle protein components, P54nrb and PSPC1, can associate with HSV-1 genomic DNA. By binding with STAT3, PSPC1 is required for the recruitment of STAT3 to paraspeckles and facilitates the interaction between STAT3 and viral gene promoters, finally increasing viral gene expression and viral replication. Furthermore, thermosensitive gel containing NEAT1 siRNA or STAT3 siRNA effectively healed the skin lesions caused by HSV-1 infection in mice. Our results provide insight into the roles of lncRNAs in the epigenetic control of viral genes and into the function of paraspeckles.