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. 2022 Jan 20;53(1):20–27. [Article in Chinese] doi: 10.12182/20220160202

表 1. Mechanism of ncRNA in regulating innate immunity.

ncRNA调控先天免疫的机制

Components of
innate immunity
Regulation mechanism of ncRNA
 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.
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].