The innate RNA sensor RIG-I is critical in the initiation of antiviral type I interferons (IFNs) production upon recognition of "non-self" viral RNAs. Here, we identify a host-derived, IFN-inducible long noncoding RNA, lnc-Lsm3b, that can compete with viral RNAs in the binding of RIG-I monomers and feedback inactivate the RIG-I innate function at late stage of innate response. Mechanistically, binding of lnc-Lsm3b restricts RIG-I protein's conformational shift and prevents downstream signaling, thereby terminating type I IFNs production. Multivalent structural motifs and long-stem structure are critical features of lnc-Lsm3b for RIG-I binding and inhibition. These data reveal a non-canonical self-recognition mode in the regulation of immune response and demonstrate an important role of an inducible "self" lncRNA acting as a potent molecular decoy actively saturating RIG-I binding sites to restrict the duration of "non-self" RNA-induced innate immune response and maintaining immune homeostasis, with potential utility in inflammatory disease management.

中文翻译：

---

RIG-I反馈对诱导型宿主lncRNA的自我识别可限制先天免疫反应。

固有的RNA传感器RIG-I在识别“非自身”病毒RNA后启动抗病毒I型干扰素（IFN）产生中至关重要。在这里，我们确定了宿主衍生的，IFN诱导的长非编码RNA，lnc-Lsm3b，可以与病毒RNA竞争RIG-I单体的结合，并且在先天性反应的后期反馈使RIG-I的先天功能失活。从机制上讲，lnc-Lsm3b的结合限制了RIG-1蛋白的构象变化并阻止了下游信号传导，从而终止了I型IFN的产生。多价结构基序和长茎结构是lnc-Lsm3b对于RIG-I结合和抑制的关键特征。这些数据揭示了在调节免疫反应中的非典型自我识别模式，并证明了诱导型“自我”的重要作用。