Interferon-Inducible LINC02605 Promotes Antiviral Innate Responses by Strengthening IRF3 Nuclear Translocation.
Interferon-Inducible LINC02605 Promotes Antiviral Innate Responses by Strengthening IRF3 Nuclear Translocation.
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干扰素诱导型 LINC02605 通过加强 IRF3 核易位促进抗病毒先天反应
DOI：
10.3389/fimmu.2021.755512
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Xu R;Yu SS;Yao RR;Tang RC;Liang JW;Pang X;Zhang J
非编码RNA是一类重要的免疫调节因子。此前，LINC 02605被确定为一个候选调节先天免疫应答的lncRNA微阵列测定。本研究系统分析了LINC 02605在天然免疫应答中的作用及其机制。RNA病毒、DNA病毒和I型IFN均以NF-κB和Jak-stat依赖方式上调LINC 02605。LINC 02605的过表达促进RNA病毒诱导的I型干扰素产生并抑制病毒复制。因此，LINC 02605的敲低导致抗病毒免疫应答降低和病毒复制增加。在机制上，LINC 02605释放了hsa-miR-107对磷酸酶和张力蛋白同源物（PTEN）表达的抑制。通过microRNA模拟物和抑制剂，证明hsa-miR-107不仅抑制PTEN的表达，而且负调节抗病毒免疫应答。LINC 02605的敲低导致PTEN在mRNA和蛋白水平上的表达降低。LINC 02605的过表达具有相反的影响。此外，LINC 02605通过促进PTEN表达减弱干扰素调节因子3（IRF 3）的丝氨酸97磷酸化水平。核质断裂试验表明，敲低LINC 02605可抑制IRF 3的核转位，使宿主细胞更容易受到病毒入侵，而过表达则表现出相反的效果。因此，LINC 02605是病毒感染诱导的lncRNA，通过调节IRF 3的核转位，在抗病毒免疫应答中发挥正反馈作用。
Non-coding RNAs represent a class of important regulators in immune response. Previously, LINC02605 was identified as a candidate regulator in innate immune response by lncRNA microarray assays. In this study, we systematically analyzed the functions and the acting mechanisms of LINC02605 in antiviral innate immune response. LINC02605 was up-regulated by RNA virus, DNA virus, and type I IFNs in NF-κB and Jak-stat dependent manner. Overexpression of LINC02605 promotes RNA virus-induced type I interferon production and inhibited viral replication. Consistently, knockdown of LINC02605 resulted in reduced antiviral immune response and increased viral replication. Mechanistically, LINC02605 released the inhibition of hsa-miR-107 on the expression of phosphatase and tensin homolog (PTEN). By microRNA mimics and inhibitors, hsa-miR-107 was demonstrated to not only inhibit PTEN’s expression but also negatively regulate the antiviral immune response. Knockdown of LINC02605 led to the reduction of PTEN expression both in mRNA and protein levels. Overexpression of LINC02605 had an opposite impact. Moreover, LINC02605 attenuated the serine 97 phosphorylation level of interferon regulatory factor 3 (IRF3) by promoting PTEN expression. Nucleoplasmic fragmentation assay showed that knocking down LINC02605 inhibited the nuclear translocation of IRF3, rendering the host cells more susceptible to viral invasion, while overexpression showed opposite effects. Therefore, LINC02605 is an induced lncRNA by viral infection and plays a positive feedback in antiviral immune response through modulating the nuclear translocation of IRF3.