Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mihai Solotchi, Smita S Patel
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引用次数: 0

Abstract

The RIG-I-like receptors (RLRs), comprising retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology 2 (LGP2), are pattern recognition receptors belonging to the DExD/H-box RNA helicase family of proteins. RLRs detect viral RNAs in the cytoplasm and respond by initiating a robust antiviral response that up-regulates interferon and cytokine production. RIG-I and MDA5 complement each other by recognizing different RNA features, and LGP2 regulates their activation. RIG-I's multilayered RNA recognition and proofreading mechanisms ensure accurate viral RNA detection while averting harmful responses to host RNAs. RIG-I's C-terminal domain targets 5'-triphosphate double-stranded RNA (dsRNA) blunt ends, while an intrinsic gating mechanism prevents the helicase domains from non-specifically engaging with host RNAs. The ATPase and RNA translocation activity of RIG-I adds another layer of selectivity by minimizing the lifetime of RIG-I on non-specific RNAs, preventing off-target activation. The versatility of RIG-I's ATPase function also amplifies downstream signaling by enhancing the signaling domain (CARDs) exposure on 5'-triphosphate dsRNA and promoting oligomerization. In this review, we offer an in-depth understanding of the mechanisms RIG-I uses to facilitate viral RNA sensing and regulate downstream activation of the immune system.

先天性免疫受体 RIG-I 的校对机制:区分自身和病毒 RNA。
RIG-I 样受体(RLRs)包括视黄酸诱导基因 I(RIG-I)、黑色素瘤分化相关基因 5(MDA5)和遗传与生理学实验室 2(LGP2),是属于 DExD/H-box RNA 螺旋酶家族的模式识别受体。RLRs 可检测到细胞质中的病毒 RNA,并通过启动强有力的抗病毒反应,上调干扰素和细胞因子的产生。RIG-I 和 MDA5 通过识别不同的 RNA 特征来相互补充,而 LGP2 则调节它们的激活。RIG-I 的多层 RNA 识别和校对机制可确保准确检测病毒 RNA,同时避免对宿主 RNA 产生有害反应。RIG-I 的 C 端结构域靶向 5'-triphosphate 双链 RNA (dsRNA) 的钝末端,而内在的门控机制可防止螺旋酶结构域与宿主 RNA 发生非特异性结合。RIG-I 的 ATPase 和 RNA 转位活性可最大限度地减少 RIG-I 在非特异性 RNA 上的停留时间,防止脱靶激活,从而增加了另一层选择性。RIG-I 的 ATPase 功能还能增强信号结构域(CARDs)在 5'-triphosphate dsRNA 上的暴露,促进寡聚化,从而扩大下游信号传导。在这篇综述中,我们将深入了解 RIG-I 用来促进病毒 RNA 感知和调节下游免疫系统激活的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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