Laboratory of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Int Immunol. 2021 Nov 25;33(12):859-865. doi: 10.1093/intimm/dxab048.
Regulation of messenger RNA (mRNA) decay plays a crucial role in the control of gene expression. Canonical mRNA decay pathways are initiated by deadenylation and decapping and are followed by exonucleolytic degradation. However, recent studies revealed that endoribonucleolytic cleavage also mediates mRNA decay, and both exoribonucleolytic and endoribonucleolytic decay pathways are important for the regulation of immune responses. Regnase-1 functions as an endoribonuclease to control immunity by damping mRNAs. Particularly, Regnase-1 controls cytokines and other inflammatory mediators by recognizing their mRNAs via stem-loop structures present in the 3' untranslated regions. Regnase-1 was found to be critical for human inflammatory diseases such as ulcerative colitis and idiopathic pulmonary fibrosis. Furthermore, a set of Regnase-1-related RNases contribute to immune regulation as well as antiviral host defense. In this review, we provide an overview of recent findings as to immune-related RNA-binding proteins (RBPs) with an emphasis on stem-loop-mediated mRNA decay via Regnase-1 and related RNases and discuss how the function of these RBPs is regulated and contributes to inflammatory disorders.
调控信使 RNA（mRNA）的降解在基因表达的调控中起着至关重要的作用。经典的 mRNA 降解途径是由去腺苷酸化和脱帽作用引发的，随后是外切核酸酶的降解。然而，最近的研究表明，内切核酸酶切割也介导了 mRNA 的降解，并且外切核酸酶和内切核酸酶降解途径对于免疫反应的调控都很重要。Regnase-1 作为一种内切核酸酶，通过阻尼 mRNAs 来控制免疫。特别是，Regnase-1 通过识别其 3'非翻译区中存在的茎环结构来控制细胞因子和其他炎症介质的 mRNA。Regnase-1 被发现对人类炎症性疾病如溃疡性结肠炎和特发性肺纤维化至关重要。此外，一组与 Regnase-1 相关的核糖核酸酶也有助于免疫调节以及抗病毒的宿主防御。在这篇综述中，我们概述了最近关于与免疫相关的 RNA 结合蛋白（RBPs）的发现，重点介绍了通过 Regnase-1 和相关的核糖核酸酶介导的茎环结构介导的 mRNA 降解，并讨论了这些 RBPs 的功能是如何被调控的，并有助于炎症性疾病。
