Stress granules (SGs) are cytoplasmic assemblies of RNA and protein that form when translation is repressed during the integrated stress response. SGs assemble from the combination of RNA-RNA, RNA-protein and protein-protein interactions between messenger ribonucleoprotein complexes (mRNPs). The protein adenosine deaminase acting on RNA 1 (ADAR1, also known as ADAR) recognizes and modifies double-stranded RNAs (dsRNAs) within cells to prevent an aberrant innate immune response. ADAR1 localizes to SGs, and since RNA-RNA interactions contribute to SG assembly and dsRNA induces SGs, we examined how ADAR1 affects SG formation. First, we demonstrate that ADAR1 depletion triggers SGs by allowing endogenous dsRNA to activate the integrated stress response through activation of PKR (also known as EIF2AK2) and translation repression. However, we also show that ADAR1 limits SG formation independently of translation inhibition. ADAR1 repression of SGs is independent of deaminase activity but is dependent on dsRNA-binding activity, suggesting a model where ADAR1 binding limits RNA-RNA and/or RNA-protein interactions necessary for recruitment to SGs. Given that ADAR1 expression is induced during viral infection, these findings have implications for the role of ADAR1 in the antiviral response. This article has an associated First Person interview with the first author of the paper.

中文翻译：

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ADAR1 通过依赖翻译和不依赖翻译的机制限制应力颗粒的形成。

应激颗粒 (SG) 是 RNA 和蛋白质的细胞质组装体，在综合应激反应过程中翻译受到抑制时形成。SGs 由信使核糖核蛋白复合物 (mRNP) 之间的 RNA-RNA、RNA-蛋白质和蛋白质-蛋白质相互作用组合而成。作用于 RNA 1 (ADAR1，也称为 ADAR) 的蛋白质腺苷脱氨酶识别并修饰细胞内的双链 RNA (dsRNA)，以防止异常的先天免疫反应。ADAR1 定位于 SG，并且由于 RNA-RNA 相互作用有助于 SG 组装并且 dsRNA 诱导 SG，我们研究了 ADAR1 如何影响 SG 形成。首先，我们证明 ADAR1 消耗通过允许内源性 dsRNA 通过激活 PKR（也称为 EIF2AK2）和翻译抑制来激活综合应激反应来触发 SG。然而，我们还表明，ADAR1 独立于翻译抑制限制了 SG 的形成。SGs 的 ADAR1 抑制不依赖于脱氨酶活性，但依赖于 dsRNA 结合活性，这表明 ADAR1 结合限制了招募 SGs 所需的 RNA-RNA 和/或 RNA-蛋白质相互作用的模型。鉴于在病毒感染期间诱导 ADAR1 表达，这些发现对 ADAR1 在抗病毒反应中的作用有影响。本文与论文的第一作者进行了相关的第一人称采访。鉴于在病毒感染期间诱导 ADAR1 表达，这些发现对 ADAR1 在抗病毒反应中的作用有影响。本文与论文的第一作者进行了相关的第一人称采访。鉴于在病毒感染期间诱导 ADAR1 表达，这些发现对 ADAR1 在抗病毒反应中的作用有影响。本文与论文的第一作者进行了相关的第一人称采访。