Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin.
Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin.
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DOI：
10.3389/fimmu.2014.00655
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发表时间：
2014
影响因子：
7.3
通讯作者：
Fortes P
中科院分区：
文献类型：
--
作者：
Barriocanal M;Carnero E;Segura V;Fortes P
许多长的非编码RNA(LncRNAs)在细胞中表达，但只有少数得到了很好的鉴定。在这些情况下，lncRNAs已被证明是几个细胞过程的关键调节因子。因此，迫切需要了解更多的lncRNAs的功能及其对刺激反应的调控。干扰素是细胞抗病毒反应的关键分子。干扰素与其受体结合可激活几个干扰素刺激基因(ISGs)的转录，这些基因可起到有效的抗病毒作用。此外，一些ISGs是干扰素途径的正性或负性调节因子。这对于确保强大的抗病毒反应和细胞稍后恢复到动态平衡至关重要。由于到目前为止所描述的ISG都是编码基因，我们试图确定干扰素是否也调节长的非编码ISG的表达。为此，我们利用核糖核酸测序技术对对照组和干扰素α-2处理的HuH7细胞的转录组进行了分析。结果表明，干扰素处理对几个未知的非编码转录本的表达有调节作用。我们已经证实了两个在不同细胞中用不同剂量的I型干扰素α2或用III型干扰素λ处理后上调的lncRNA。流感和水泡性口炎病毒突变株不能阻断干扰素反应，但不能被几种野生型裂解病毒诱导，也能诱导这些lncRNAs。这些lncRNA基因被命名为lncISG15和lncBST2，因为它们分别位于ISG ISG15和BST2附近。有趣的是，抑制实验表明，lncBST2是BST2的正调控因子。因此，将lncBST2改名为BISPR，由BST2干扰素刺激的正性调节因子改名为BISPR。我们的结果可能具有治疗意义，因为在感染丙型肝炎病毒的细胞和感染患者的肝脏中，lncBST2/BISPR，但也增加了lncISG15及其编码的邻居。这些结果允许我们假设几个lncRNAs可以被干扰素激活来控制抗病毒干扰素反应的效力。
Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response.
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影响因子：
14.9
作者：
Abad X;Razquin N;Abad A;Fortes P
通讯作者：
Fortes P
影响因子：
32.4
作者：
Blanco-Melo D;Venkatesh S;Bieniasz PD
通讯作者：
Bieniasz PD
影响因子：
14.9
作者：
Blazquez, Lorea;Jovanna Gonzalez-Rojas, Sandra;Fortes, Puri
通讯作者：
Fortes, Puri
DOI：
10.1126/science.1240925
发表时间：
2013-08-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carpenter S;Aiello D;Atianand MK;Ricci EP;Gandhi P;Hall LL;Byron M;Monks B;Henry-Bezy M;Lawrence JB;O'Neill LA;Moore MJ;Caffrey DR;Fitzgerald KA
通讯作者：
Fitzgerald KA
影响因子：
5.4
作者：
Bigger, CB;Guerra, B;Lanford, RE
通讯作者：
Lanford, RE