据介绍，RIG-I 样受体 (RLR) 下游的抗病毒信号传导通过围绕衔接蛋白线粒体抗病毒信号蛋白 (MAVS) 组织的多蛋白复合物进行。蛋白质复合物的功能可以通过提供变构调节或充当分子向导或支架的 RNA 分子进行调节。
研究人员假设 RNA 在组织 MAVS 信号传导平台中发挥作用。研究人员发现 MAVS 通过其中心内在无序域直接与细胞mRNA 的 3' 非翻译区相互作用。通过核糖核酸酶处理消除 RNA 会破坏 MAVS 信号体，包括调节 RLR 信号传导和病毒限制的 RNA 调节的 MAVS 相互作用物，并抑制诱导干扰素的转录因子的磷酸化。
总之，这一研究揭示了细胞 RNA 在通过 MAVS 促进信号传导方面的作用，并强调了 RNA 调节免疫信号复合物的普遍原理。
附：英文原文
Title: Cellular RNA interacts with MAVS to promote antiviral signaling
Author: Nandan S. Gokhale, Russell K. Sam, Kim Somfleth, Matthew G. Thompson, Daphnée M. Marciniak, Julian R. Smith, Emmanuelle Genoyer, Julie Eggenberger, Lan H. Chu, Moonhee Park, Steve Dvorkin, Andrew Oberst, Stacy M. Horner, Shao-En Ong, Michael GaleJr., Ram Savan
Issue&Volume: 2024-12-20
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.
DOI: adl0429
Source: https://www.science.org/doi/10.1126/science.adl0429