The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers
The Nuclear Matrix Protein SAFA Surveils Viral RNA and Facilitates Immunity by Activating Antiviral Enhancers and Super-enhancers
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核基质蛋白 SAFA 监视病毒 RNA 并通过激活抗病毒增强剂和超级增强剂促进免疫
DOI：
10.1016/j.chom.2019.08.010
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发表时间：
2019-09-11
影响因子：
30.3
通讯作者：
You, Fuping
中科院分区：
文献类型：
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作者：
Cao, Lili;Liu, Shengde;You, Fuping
病原体模式识别受体（PRRs）触发对入侵病原体的先天免疫应答。所有已知的病毒RNA的PRR都具有核内定位。然而，对于许多病毒，复制在细胞核中产生dsRNA。在这里，我们表明，核基质蛋白SAFA（也称为HnRNPU）的功能作为一个核病毒的DNA和RNA病毒的dsRNA传感器。在识别病毒dsRNA后，SAFA寡聚化并激活抗病毒基因的增强子，包括IFNB 1。此外，SAFA是激活超级增强子所必需的，超级增强子指导强有力的免疫基因转录以建立抗病毒状态。骨髓特异性SAFA缺陷小鼠更容易受到致命的HSV-1和VSV感染，I型IFN减少。因此，SAFA作为核病毒RNA传感器和反式激活剂发挥作用，以桥接先天传感与染色质重塑，并增强强大的抗病毒反应。
Pathogen pattern recognition receptors (PRRs) trigger innate immune responses to invading pathogens. All known PRRs for viral RNA have extranuclear localization. However, for many viruses, replication generates dsRNA in the nucleus. Here, we show that the nuclear matrix protein SAFA (also known as HnRNPU) functions as a nuclear viral dsRNA sensor for both DNA and RNA viruses. Upon recognition of viral dsRNA, SAFA oligomerizes and activates the enhancers of antiviral genes, including IFNB1. Moreover, SAFA is required for the activation of super-enhancers, which direct vigorous immune gene transcription to establish the antiviral state. Myeloid-specific SAFA-deficient mice were more susceptible to lethal HSV-1 and VSV infection, with decreased type I IFNs. Thus, SAFA functions as a nuclear viral RNA sensor and trans-activator to bridge innate sensing with chromatin remodeling and potentiate robust antiviral responses.