Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue Cleveland, OH 44195, USA.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue Cleveland, OH 44195, USA; Pediatrics Division Office, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA(1).
Cytokine. 2020 Sep;133:153847. doi: 10.1016/j.cyto.2016.08.009. Epub 2016 Aug 29.
Ever since the discovery of the existence of an interferon (IFN)-regulated ribonuclease, significant advances have been made in understanding the mechanism and associated regulatory effects of its action. What had been studied initially as a "unique" endoribonuclease is currently known as ribonuclease L (RNase L where "L" stands for latent). Some of the key developments include discovery of the RNase L signaling pathway, its structural characterization, and its molecular cloning. RNase L has been implicated in antiviral and antibacterial defense, as well as in hereditary prostate cancer. RNase L is activated by 2'-5' linked oligoadenylates (2-5A), which are synthesized by the oligoadenylate synthetases (OASs), a family of IFN-regulated pathogen recognition receptors that sense double-stranded RNAs. Activated RNase L cleaves single stranded RNAs, including viral RNAs and cellular RNAs. The catalytic activity of RNase L has been found to lead into the activation of several cellular signaling pathways, including those involved in autophagy, apoptosis, IFN-β production, NLRP3 inflammasome activation leading to IL-1β secretion, inhibition of cell migration, and cell adhesion. In this review, we will highlight the newest advances in our understanding of the catalytic role of RNase L in the context of different cellular pathways and extend the scope of these findings to discussion of potential therapeutic targets for antimicrobial drug development.
自干扰素（IFN）调节的核糖核酸酶的存在被发现以来，人们在理解其作用的机制和相关调节效应方面取得了重大进展。最初作为“独特”的内切核糖核酸酶进行研究的物质，现在被称为核糖核酸酶 L（RNase L，其中“L”代表潜伏）。一些关键的发展包括发现 RNase L 信号通路、其结构特征及其分子克隆。RNase L 参与抗病毒和抗菌防御，以及遗传性前列腺癌。RNase L 被 2'-5' 连接寡腺苷酸（2-5A）激活，2-5A 由寡腺苷酸合成酶（OAS）合成，OAS 是一组 IFN 调节的病原体识别受体，可识别双链 RNA。激活的 RNase L 切割单链 RNA，包括病毒 RNA 和细胞 RNA。已经发现 RNase L 的催化活性会导致几种细胞信号通路的激活，包括自噬、细胞凋亡、IFN-β 产生、NLRP3 炎性小体激活导致 IL-1β 分泌、抑制细胞迁移和细胞黏附。在这篇综述中，我们将重点介绍我们在理解 RNase L 在不同细胞途径中的催化作用方面的最新进展，并将这些发现的范围扩展到讨论抗菌药物开发的潜在治疗靶点。
