Non-Coding RNA and Innate Immune Signal Regulation
摘要: 先天免疫对消除和控制感染至关重要，但不受控制的免疫反应可损伤宿主组织。机体免疫稳态的调节是一个精确的、复杂的过程，其中，非编码RNA是多种生物过程中的重要调控因子。目前研究表明微小RNA、长链非编码RNA通过调控先天免疫途径中的基因表达参与抗病毒反应、肿瘤免疫及自身免疫性疾病。通常情况下，微小RNA通过与mRNA的3′端非翻译区结合，在转录后水平调节基因表达，而长链非编码RNA则作为微小RNA的内源竞争RNA，抑制微小RNA与信使RNA的结合，发挥免疫调控作用。本综述总结了非编码RNA在先天免疫中的调节作用及其机制，为先天免疫的调节及免疫相关疾病的研究提供参考。同时，koko体育app 也展望了该领域未来的研究方向，包括新型非编码RNA的表达与成熟调控机制，以及非编码RNA在进化中的保守性等。Abstract: The innate immune system is critical to the elimination and control of infections. However, uncontrolled immune responses can cause indirect host-mediated tissue damage. The regulation of immune homeostasis is a complex but finely regulated process. ncRNAs have been increasingly identified as important regulators of a variety of biological processes. Recent research findings suggest that microRNAs and long non-coding RNAs participate in antiviral responses, tumor immunity, and autoimmune diseases by regulating gene expression in the innate immune pathways. MicroRNAs regulate gene expression at the post-transcriptional level by binding to the 3′ untranslated regions of mRNA, while long non-coding RNAs act as endogenous competing RNAs for microRNAs, inhibiting the binding of microRNAs and mRNAs. In this review, we summarized the regulatory role of non-coding RNAs in innate immunity and its mechanism to provide references for research in the regulation of innate immunity and immune-related diseases. In addition, we also reported discussions on the future research directions in the field, including the expression and maturation regulation mechanism of new non-coding RNAs, and the conservation of non-coding RNAs in evolution.
图 2 ncRNA调控IRF3
Figure 2. 🌼 The regulatory mechanism of ncRNA on IRF3TLR: Toll-like receptor; TIR: Toll/IL-1R; TIRAP: TIR domain containing adaptor protein; IRAKs: IL-1 receptor associated kinase; TRAF: Tumor necrosis factor receptor-associated factor; IKKs: Inhibitor of NF-κB kinase complex; MAPKs: Mitogen-activated protein kinases; TBK1: TANK-binding kinase 1; IKKi: Inducible IκB Kinase; RIP1: Receptor-interacting protein 1; TAK1: Transforming growth factor β-activated kinase 1; TRAM: TRIF-related adaptor molecule; TRIF: TIR-domain-containing adaptor protein inducing IFN-β; OPTN: Optineurin; IRF: Interferon regulatory factor; PP2A: Protein phosphatase 2A; IFN: Interferon.
表 1 ncRNA调控先天免疫的机制
Table 1. ♚ Mechanism of ncRNA in regulating innate immunity
Regulation mechanism of ncRNA IRF ① miRNA: Directly binds to the 3′UTR of IRF mRNA and inhibits its expression; indirectly inhibits phosphorylation of IRF; inhibits the expression of upstream molecules of IRF, thereby inhibiting IRF. ② lncRNA: Competitively binds to miRNA to inhibit the binding of miRNA to target gene, thereby blocking miRNA function; competes with IRF3 to bind to the IFN-β promoter, interfering with the binding of IRF3 and IFN-β; binds to TBK1 kinase ubiquitination adaptor OPTN and stabilizes OPTN, promoting TLR-TBK1-dependent IRF3 phosphorylation. TRIF ① miRNA: Directly binds to the 3′UTR of TRIF mRNA and inhibits its expression. ② circRNA: Interacts with miRNA as a competitive endogenous RNA of TRIF mRNA. RIG-Ⅰ ① miRNA: Inhibits the expression of RIG-Ⅰ ubiquitination regulator TRIM25, thereby inhibiting the ubiquitination of RIG-Ⅰ; targets the 3′UTR of RIG-Ⅰ encoding gene DDX58 to inhibit the expression of RIG-Ⅰ; functions as ligand of RIG-Ⅰ, thereby contributing to immune enhancement. ② lncRNA: Competitively binds to the CTD of RIG-Ⅰ with viral RNA and limits its protein conformational changes, leaving RIG-Ⅰ in an inactive state; eliminates SFPQ’s transcription inhibitory effect on RIG-Ⅰ. M AVS ① miRNA: Directly binds to the 3′UTR of MAVS mRNA and inhibits its expression; indirectly regulates MAVS by targeting mitochondrial transporter. ② lncRNA: Competitively binds to miRNA, thereby blocking miRNA function. cGA S ① miRNA: Directly binds to the 3′UTR of cGAS mRNA and inhibits its expression; suppresses the mRNA level of cGAS by acting on epigenetic factors that maintain the expression of cGAS. ② lncRNA: Indirectly regulates the cGAS pathway by participating in the assembly of the HDP-RNP. STING ① miRNA: Directly binds to the 3′UTR of STING mRNA and inhibits its expression. ② lncRNA: Indirectly regulates STING transcription through CREB. ncRNA: Non-coding RNA; IRF: Interferon regulatory factor; miRNA: MicroRNA; 3′UTR: 3′ untranslated regions; lncRNA: Long non-coding RNA; IFN-β: Interferon-β; TBK1: TANK-bindingkinase; OPTN: Optineurin; TLR: Toll-like receptor; TRIF: TIR-domain-containing adaptor inducing interferon-β; circRNA: Circular RNA; RIG-Ⅰ: Retinoic acid‐inducible gene Ⅰ; TRIM25: Tripartite motif-containing protein 25; CTD: C-terminal domain; SFPQ: Splicing factor proline-and glutamine-rich protein; MAVS: Mitochondrial antiviral signaling; cGAS: Cyclic GMP-AMP synthase; HDP-RNP: HEXIM1-DNA-PK-paraspeckle components-ribonu-cleoprotein complex; STING: Stimulator of interferon genes; CREB: cAMP response element-binding protein.
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