非编码RNA与先天免疫信号调控

仇学梅; 李鑫; 刘锐

doi:10.12182/20220160202

非编码RNA与先天免疫信号调控

doi:

耳鼻喉肠道疾患深入分析地方侧重调查室地方耳鼻喉肠道疾患临床治疗生物学深入分析管理中心广东大学生华西耳鼻喉医疗（成都市 610041）

基金项目: 四川省科技厅项目（No. 2020YFSY0009）资助

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通讯作者:
E-mail: liurui_scu@hotmail.com

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出版历程
- 收稿日期: 2022-09-20
- 修回日期: 2022-12-09
- 网络出版日期: 2023-01-24
- 刊出日期: 2023-01-24

Non-Coding RNA and Innate Immune Signal Regulation

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China

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Corresponding author: E-mail: liurui_scu@hotmail.com

摘要

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。
- 先天免疫 /
- 非编码RNA /
- 微小RNA /
- 长链非编码RNA
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.
- Innate immune /
- ncRNA /
- miRNA /
- lncRNA

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图 1 非编码RNA的生物合成

Figure 1. Biosynthesis of non-coding RNA

miRNA: MicroRNA; mRNA: Messenger RNA; circRNA: Circular RNA; lncRNA: Long non-coding RNA; piRNA: PIWI-interacting RNA; tRNA: Transfer RNA; tsRNA: Transfer RNA-derived small RNA.

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图 2 ncRNA调控IRF3

Figure 2. 🌃 The regulatory mechanism of ncRNA on IRF3

TLR: 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.

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表 1 ncRNA调控先天免疫的机制

Table 1. ౠ Mechanism of ncRNA in regulating innate immunity

Components of innate immunity	Regulation mechanism of ncRNA
IRF	① miRNA: Directly binds to the 3′UTR of IRF mRNA and inhibits its expression^[26]; indirectly inhibits phosphorylation of 　IRF^[27]; inhibits the expression of upstream molecules of IRF, thereby inhibiting IRF^[28].
IRF	② lncRNA: Competitively binds to miRNA to inhibit the binding of miRNA to target gene, thereby blocking miRNA function^[29]; competes with IRF3 to bind to the IFN-β promoter, interfering with the binding of IRF3 and IFN-β^[30]; binds to TBK1 kinase ubiquitination adaptor OPTN and stabilizes OPTN, promoting TLR-TBK1-dependent IRF3 phosphorylation^[31].
TRIF	① miRNA: Directly binds to the 3′UTR of TRIF mRNA and inhibits its expression^[32].
TRIF	② circRNA: Interacts with miRNA as a competitive endogenous RNA of TRIF mRNA^[32].
RIG-Ⅰ	① miRNA: Inhibits the expression of RIG-Ⅰ ubiquitination regulator TRIM25, thereby inhibiting the ubiquitination of RIG-Ⅰ^[33]; targets the 3′UTR of RIG-Ⅰ encoding gene DDX58 to inhibit the expression of RIG-Ⅰ^[34]; functions as ligand of RIG-Ⅰ, thereby contributing to immune enhancement^[35].
RIG-Ⅰ	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^[36]; eliminates SFPQ’s transcription inhibitory effect on RIG-Ⅰ^[37].
MAVS	① miRNA: Directly binds to the 3′UTR of MAVS mRNA and inhibits its expression^[38]; indirectly regulates MAVS by targeting mitochondrial transporter^[39].
MAVS	② lncRNA: Competitively binds to miRNA, thereby blocking miRNA function^[40].
cGAS	① miRNA: Directly binds to the 3′UTR of cGAS mRNA and inhibits its expression^[41]; suppresses the mRNA level of cGAS by acting on epigenetic factors that maintain the expression of cGAS^[42].
cGAS	② lncRNA: Indirectly regulates the cGAS pathway by participating in the assembly of the HDP-RNP^[3].
STING	① miRNA: Directly binds to the 3′UTR of STING mRNA and inhibits its expression^[43].
STING	② lncRNA: Indirectly regulates STING transcription through CREB^[44].
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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