Dynamic changes in gene expression are key factors in the development and activation of immune cells. RNA metabolism is one of the critical steps for the control of gene expression. Together with transcriptional regulation, mRNA decay by specific ribonucleases (RNases) plays a vital role in shaping gene expression. In addition to the canonical exoribonuclease-mediated mRNA degradation through the recognition of cis-elements in mRNA 3′ untranslated regions by RNA-binding proteins (RBPs), endoribonucleases are involved in the control of mRNAs in immune cells. In this review, we gleam insights on how Regnase-1, an endoribonuclease necessary for regulating immune cell activation and maintenance of immune homeostasis, degrades RNAs involved in immune cell activation. Additionally, we provide insights on recent studies which uncover the role of Regnase-1–related RNases, including Regnase-2, Regnase-3, and Regnase-4, as well as N4BP1 and KHNYN, in immune regulation and antiviral immunity. As the dysregulation of immune mRNA decay leads to pathologies such as autoimmune diseases or impaired activation of immune responses, RNases are deemed as essential components of regulatory feedback mechanisms that modulate inflammation. Given the critical role of RNases in autoimmunity, RNases can be perceived as emerging targets in the development of novel therapeutics.

中文翻译：

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健康和免疫疾病中的 Regnase-1 相关核糖核酸内切酶

基因表达的动态变化是免疫细胞发育和激活的关键因素。RNA代谢是控制基因表达的关键步骤之一。与转录调控一起，特定核糖核酸酶 (RNases) 导致的 mRNA 衰变在塑造基因表达中起着至关重要的作用。除了通过识别顺式的经典外切核糖核酸酶介导的 mRNA 降解通过 RNA 结合蛋白 (RBP) 在 mRNA 3' 非翻译区中的元件，核糖核酸内切酶参与免疫细胞中 mRNA 的控制。在这篇综述中，我们对 Regnase-1（一种调节免疫细胞活化和维持免疫稳态所必需的核糖核酸内切酶）如何降解参与免疫细胞活化的 RNA 进行了深入研究。此外，我们提供了对近期研究的见解，这些研究揭示了 Regnase-1 相关的 RNases，包括 Regnase-2、Regnase-3 和 Regnase-4，以及 N4BP1 和 KHNYN，在免疫调节和抗病毒免疫中的作用。由于免疫 mRNA 衰变的失调会导致自身免疫性疾病或免疫反应激活受损等疾病，因此 RNase 被认为是调节炎症的调节反馈机制的重要组成部分。