Cellular RNA interacts with MAVS to promote antiviral signaling

Abstract

Antiviral signaling downstream of RIG-I–like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides or scaffolds. We hypothesized that RNA plays a role in organizing MAVS signaling platforms. We found that MAVS, through its central intrinsically disordered domain, directly interacted with the 3′ untranslated regions of cellular messenger RNAs. Elimination of RNA by ribonuclease treatment disrupted the MAVS signalosome, including RNA-modulated MAVS interactors that regulate RLR signaling and viral restriction, and inhibited phosphorylation of transcription factors that induce interferons. This work uncovered a function for cellular RNA in promoting signaling through MAVS and highlights generalizable principles of RNA regulatory control of immune signaling complexes.

RIG-I 样受体 （RLR） 下游的抗病毒信号转导通过围绕衔接蛋白线粒体抗病毒信号转导蛋白 （MAVS） 组织的多蛋白复合物进行。蛋白质复合物功能可以由提供变构调节或充当分子向导或支架的 RNA 分子调节。我们假设 RNA 在组织 MAVS 信号转导平台中发挥作用。我们发现 MAVS 通过其中央内在无序结构域直接与细胞信使 RNA 的 3' 非翻译区相互作用。通过核糖核酸酶处理消除 RNA 破坏了 MAVS 信号体，包括调节 RLR 信号传导和病毒限制的 RNA 调节的 MAVS 相互作用器，并抑制了诱导干扰素的转录因子的磷酸化。这项工作揭示了细胞 RNA 通过 MAVS 促进信号传导的功能，并强调了免疫信号复合物 RNA 调节控制的可推广原则。

References and notes
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