Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
mBio. 2013 Jan 29;4(1):e00596-12. doi: 10.1128/mBio.00596-12.
Most of the human genome is transcribed into protein-noncoding RNAs (ncRNAs), including small ncRNAs and long ncRNAs (lncRNAs). Over the past decade, rapidly emerging evidence has increasingly supported the view that lncRNAs serve key regulatory and functional roles in mammal cells. HIV-1 replication relies on various cell functions. To date, while the involvement of host protein factors and microRNAs (miRNAs) in the HIV-1 life cycle has been extensively studied, the relationship between lncRNAs and HIV-1 remains uncharacterized. Here, we have profiled 83 disease-related lncRNAs in HIV-1-infected T cells. We found NEAT1 to be one of several lncRNAs whose expression is changed by HIV-1 infection, and we have characterized its role in HIV-1 replication. We In the abstract, added definition of INS OK, or should "cis-acting" be added?report here that the knockdown of NEAT1 enhances virus production through increased nucleus-to-cytoplasm export of Rev-dependent instability element (INS)-containing HIV-1 mRNAs. IMPORTANCE Long protein-noncoding RNAs (lncRNAs) play roles in regulating gene expression and modulating protein activities. There is emerging evidence that lncRNAs are involved in the replication of viruses. To our knowledge, this report is the first to characterize a role contributed by an lncRNA, NEAT1, to HIV-1 replication. NEAT1 is essential for the integrity of the nuclear paraspeckle substructure. Based on our findings from NEAT1 knockdown, we have identified the nuclear paraspeckle body as another important subcellular organelle for HIV-1 replication.
人类基因组的大部分都被转录为蛋白质非编码 RNA(ncRNA),包括小 ncRNA 和长 ncRNA(lncRNA)。在过去的十年中,越来越多的新证据支持这样一种观点,即 lncRNA 在哺乳动物细胞中发挥关键的调节和功能作用。HIV-1 的复制依赖于各种细胞功能。迄今为止,尽管宿主蛋白因子和 microRNAs(miRNAs)在 HIV-1 生命周期中的作用已得到广泛研究,但 lncRNA 与 HIV-1 之间的关系尚未确定。在这里,我们对 HIV-1 感染的 T 细胞中的 83 种疾病相关 lncRNA 进行了分析。我们发现 NEAT1 是几种受 HIV-1 感染而改变表达的 lncRNA 之一,并对其在 HIV-1 复制中的作用进行了描述。我们在此报告,敲低 NEAT1 通过增加 Rev 依赖性不稳定元件(INS)包含的 HIV-1 mRNA 的核质输出,增强了病毒的产生。重要的是,长蛋白非编码 RNA(lncRNA)在调节基因表达和调节蛋白活性方面发挥作用。有新的证据表明,lncRNA 参与了病毒的复制。据我们所知,这是首次描述 lncRNA NEAT1 对 HIV-1 复制的作用。NEAT1 是核斑结构亚基完整性所必需的。基于我们从 NEAT1 敲低实验中得到的结果,我们确定了核斑体是 HIV-1 复制的另一个重要的亚细胞细胞器。