The heterogeneous nuclear ribonucleoprotein hnRNPM inhibits RNA virus-triggered innate immunity by antagonizing RNA sensing of RIG-I-like receptors
The heterogeneous nuclear ribonucleoprotein hnRNPM inhibits RNA virus-triggered innate immunity by antagonizing RNA sensing of RIG-I-like receptors
复制标题
异质核核糖核蛋白 hnRNPM 通过拮抗 RIG-I 样受体的 RNA 感应来抑制 RNA 病毒触发的先天免疫
DOI：
10.1371/journal.ppat.1007983
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发表时间：
2019-08-01
期刊：
影响因子：
6.7
通讯作者：
Li, Shu
中科院分区：
文献类型：
--
作者：
Cao, Pan;Luo, Wei-Wei;Li, Shu
视黄酸诱导基因-I（RIG-I）样受体（RLR）（包括RIG-I和MDA 5）识别病毒RNA启动先天性抗病毒应答。尽管已经广泛地研究了RLRs介导的信号转导的调节，但是如何调节RLRs对病毒RNA的识别仍然是个谜。在这项研究中，我们确定了异质核核糖核蛋白M（hnRNPM）作为一个负调节器的TLR介导的信号。hnRNPM的过表达显著抑制RNA病毒引发的先天免疫反应。相反，hnRNPM缺陷增加了病毒RNA触发的先天免疫应答，并抑制了RNA病毒的复制。病毒感染引起hnRNPM从细胞核易位到细胞质。hnRNPM与RIG-I和MDA 5相互作用，并破坏RLRs与病毒RNA的结合，导致先天性抗病毒反应的抑制。我们的研究结果表明，hnRNPM作为一个重要的诱饵过度的先天性抗病毒免疫反应。
Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and MDA5, initiates innate antiviral responses. Although regulation of RLR-mediated signal transduction has been extensively investigated, how the recognition of viral RNA by RLRs is regulated remains enigmatic. In this study, we identified heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a negative regulator of RLR-mediated signaling. Overexpression of hnRNPM markedly inhibited RNA virus-triggered innate immune responses. Conversely, hnRNPM-deficiency increased viral RNA-triggered innate immune responses and inhibited replication of RNA viruses. Viral infection caused translocation of hnRNPM from the nucleus to the cytoplasm. hnRNPM interacted with RIG-I and MDA5, and impaired the binding of the RLRs to viral RNA, leading to inhibition of innate antiviral response. Our findings suggest that hnRNPM acts as an important decoy for excessive innate antiviral immune response.