Laboratory of Infection and Prevention, Institute for Frontier Life and Medical Sciences, Kyoto University, AMED-CREST, AMED, Kyoto, Japan.
Wiley Interdiscip Rev RNA. 2018 Jan;9(1). doi: 10.1002/wrna.1449. Epub 2017 Sep 20.
The activation of inflammatory cells is controlled at transcriptional and posttranscriptional levels. Posttranscriptional regulation modifies mRNA stability and translation, allowing for elaborate control of proteins required for inflammation, such as proinflammatory cytokines, prostaglandin synthases, cell surface co-stimulatory molecules, and even transcriptional modifiers. Such regulation is important for coordinating the initiation and resolution of inflammation, and is mediated by a set of RNA-binding proteins (RBPs), including Regnase-1, Roquin, Tristetraprolin (TTP), and AU-rich elements/poly(U)-binding/degradation factor 1 (AUF1). Among these, Regnase-1, also known as Zc3h12a and Monocyte chemotactic protein-1-induced protein-1 (MCPIP1), acts as an endoribonuclease responsible for the degradation of mRNAs involved in inflammatory responses. Conversely, the RBPs Roquin and TTP trigger exonucleolytic degradation of mRNAs by recruiting the CCR4-NOT deadenylase complex. Regnase-1 specifically recognizes stem-loop structures present in 3'-untranslated regions of cytokine mRNAs, and directly degrades the mRNAs in a translation- and ATP-dependent RNA helicase upframeshift 1 (UPF1)-dependent manner that is reminiscent of nonsense-mediated decay. Regnase-1 regulates the activation of innate and acquired immune cells, and is critical for maintaining immune homeostasis as well as preventing over-activation of the immune system under inflammatory conditions. Furthermore, recent studies have revealed that Regnase-1 and its family members are involved not only in immunity but also in various biological processes. In this article, I review molecular mechanisms of Regnase-1-mediated mRNA decay and its physiological roles. WIREs RNA 2018, 9:e1449. doi: 10.1002/wrna.1449 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications RNA Turnover and Surveillance > Regulation of RNA Stability RNA in Disease and Development > RNA in Disease.
炎症细胞的激活受到转录和转录后水平的控制。转录后调控可调节 mRNA 的稳定性和翻译，从而对炎症所需的蛋白质进行精细调控，如促炎细胞因子、前列腺素合酶、细胞表面共刺激分子，甚至转录修饰因子。这种调控对于协调炎症的启动和解决至关重要，是由一组 RNA 结合蛋白（RBPs）介导的，包括 Regnase-1、Roquin、Tristetraprolin（TTP）和富含 AU 元件/多（U）结合/降解因子 1（AUF1）。在这些蛋白中，Regnase-1，也称为 Zc3h12a 和单核细胞趋化蛋白-1 诱导蛋白-1（MCPIP1），作为一种内切核酸酶，负责降解参与炎症反应的 mRNA。相反，RBPs Roquin 和 TTP 通过招募 CCR4-NOT 脱腺苷酸酶复合物触发 mRNA 的外切核酸酶降解。Regnase-1 特异性识别细胞因子 mRNA 3'-非翻译区中存在的茎环结构，并以翻译和 ATP 依赖性 RNA 解旋酶 UPF1 依赖性方式直接降解 mRNA，类似于无意义介导的衰变。Regnase-1 调节先天和获得性免疫细胞的激活，对于维持免疫稳态以及在炎症条件下防止免疫系统过度激活至关重要。此外，最近的研究表明，Regnase-1 及其家族成员不仅参与免疫，还参与各种生物过程。本文综述了 Regnase-1 介导的 mRNA 降解的分子机制及其生理作用。WIREs RNA 2018, 9:e1449. doi: 10.1002/wrna.1449 本文分类为： RNA 与蛋白质和其他分子的相互作用 > 蛋白质-RNA 相互作用：功能意义 RNA 周转和监测 > RNA 稳定性的调节 RNA 在疾病和发育中的作用 > RNA 在疾病中的作用。
