The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response.
The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response.
复制标题
DOI：
10.3390/ijms17010074
复制
发表时间：
2016-01-08
影响因子：
5.6
通讯作者：
Hassel BA
中科院分区：
文献类型：
--
作者：
Ezelle HJ;Malathi K;Hassel BA
干扰素调节的核糖核酸内切酶-L参与了抗菌天然免疫反应的多个方面。它是核糖核酸裂解途径的末端成分，在该途径中，dsRNA通过2‘-5’-寡腺苷合成酶诱导产生核糖核酸酶-L激活2-5A。然后，活性核酸酶切割单链RNA，包括细胞和病毒，导致它们的表达下调，并产生能够激活维甲酸诱导基因-I(RIG-I)样受体或核苷酸结合的寡聚化结构域样受体3(NLRP3)炎症体的小RNA。这导致干扰素β的表达和IL-1β的激活，以及对免疫细胞功能的更广泛的影响。核糖核酸酶-L也是越来越多的与细胞骨架相互作用的天然免疫成分之一。它可以与几种细胞骨架蛋白结合，包括丝蛋白A，一种与核糖核酸酶-L合作维持细胞屏障以阻止病毒进入的肌动蛋白结合蛋白。这种抗病毒活性不依赖于催化功能，这是RNase-L的独特机制。我们还描述了核糖核酸酶-L与E3泛素连接酶和支架蛋白的相互作用，Nump蛋白X(Lnx)的配体是紧密连接蛋白的调节因子。为了更好地理解这些新的结合伙伴在抗菌反应中的意义和背景，还讨论了其他天然免疫蛋白与细胞骨架的相互作用。
The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2′-5′-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.