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非项目编码RNA与先天不足免疫抗体信息改善

仇学梅 李鑫 刘锐

仇学梅, 李鑫, 刘锐. 非编码RNA与先天免疫信号调控[J]. koko体育app 学报(医学版), 2022, 53(1): 20-27. doi: 10.12182/20220160202
引用本文: 仇学梅, 李鑫, 刘锐. 非编码RNA与先天免疫信号调控[J]. koko体育app 学报(医学版), 2022, 53(1): 20-27. doi:
QIU Xue-mei, LI Xin, LIU Rui. Non-Coding RNA and Innate Immune Signal Regulation[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2022, 53(1): 20-27. doi: 10.12182/20220160202
Citation: QIU Xue-mei, LI Xin, LIU Rui. Non-Coding RNA and Innate Immune Signal Regulation[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2022, 53(1): 20-27. doi:

非编码RNA与先天免疫信号调控

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基金项目: 四川省科技厅项目(No. 2020YFSY0009)资助
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    E-mail: liurui_scu@hotmail.com

Non-Coding RNA and Innate Immune Signal Regulation

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  • 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。
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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.

    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.

    表  1  ncRNA调控先天免疫的机制

    Table  1.   ♚ 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].
    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].
    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].
    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].
    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].
    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].
    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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  • 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

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