RIG-I is our first line of defense against RNA viruses, serving as a pattern recognition receptor that identifies molecular features common among dsRNA and ssRNA viral pathogens. RIG-I is maintained in an inactive conformation as it samples the cellular space for pathogenic RNAs. Upon encounter with the triphosphorylated terminus of blunt-ended viral RNA duplexes, the receptor changes conformation and releases a pair of signaling domains (CARDs) that are selectively modified and interact with an adapter protein (MAVS), thereby triggering a signaling cascade that stimulates transcription of interferons. Here, we describe the structural determinants for specific RIG-I activation by viral RNA, and we describe the strategies by which RIG-I remains inactivated in the presence of host RNAs. From the initial RNA triggering event to the final stages of interferon expression, we describe the experimental evidence underpinning our working knowledge of RIG-I signaling. We draw parallels with behavior of related proteins MDA5 and LGP2, describing evolutionary implications of their collective surveillance of the cell. We conclude by describing the cell biology and immunological investigations that will be needed to accurately describe the role of RIG-I in innate immunity and to provide the necessary foundation for pharmacological manipulation of this important receptor.

中文翻译：

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RIG-I激活和信号传导的分子机制

RIG-I 是我们抵御 RNA 病毒的第一道防线，作为一种模式识别受体，可识别 dsRNA 和 ssRNA 病毒病原体中常见的分子特征。RIG-I 在对病原性 RNA 的细胞空间进行采样时保持在非活性构象中。在遇到平端病毒 RNA 双链体的三磷酸化末端后，受体会改变构象并释放一对信号结构域 (CARD)，这些结构域被选择性修饰并与接头蛋白 (MAVS) 相互作用，从而触发刺激转录的信号级联反应的干扰素。在这里，我们描述了病毒 RNA 激活特定 RIG-I 的结构决定因素，并描述了在宿主 RNA 存在下 RIG-I 保持失活的策略。从最初的 RNA 触发事件到干扰素表达的最后阶段，我们描述了支持我们对 RIG-I 信号传导的工作知识的实验证据。我们与相关蛋白 MDA5 和 LGP2 的行为相提并论，描述了它们对细胞的集体监视的进化意义。最后，我们描述了准确描述 RIG-I 在先天免疫中的作用并为这一重要受体的药理学操作提供必要基础所需的细胞生物学和免疫学研究。