Non-Coding RNA and Innate Immune Signal Regulation
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.
Keywords: Innate immune, ncRNA, miRNA, lncRNA
Full Text:
PDFReferences
SLACK F J, CHINNAIYAN A M. The role of non-coding RNAs in oncology. Cell,2019,179(5): 1033–1055.
WANG J, ZHU S, MENG N, et al. ncRNA-encoded peptides or proteins and cancer. Mol Ther,2019,27(10): 1718–1725.
MORCHIKH M, CRIBIER A, RAFFEL R, et al. HEXIM1 and NEAT1 long non-coding RNA form a multi-subunit complex that regulates DNA-mediated innate immune response. Mol Cell, 2017, 67(3): 387–399.e385[2021-08-21]. https://doi.org/10.1016/j.molcel.2017.06.020.
SALMENA L, POLISENO L, TAY Y, et al. A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell,2011,146(3): 353–358.
HUANG X, FEJES TÓTH K, ARAVIN A A. piRNA biogenesis in drosophila melanogaster. Trends Genet,2017,33(11): 882–894.
CHEN X, YANG T, WANG W, et al. Circular RNAs in immune responses and immune diseases. Theranostics,2019,9(2): 588–607.
KIM J K, KIM T S, BASU J, et al. MicroRNA in innate immunity and autophagy during mycobacterial infection. Cell Microbiol, 2017, 19(1): e12687[2021-08-21]. https://doi.org/10.1111/cmi.12687.
WANG Y, WANG Y, LUO W, et al. Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses. Theranostics,2020,10(20): 9407–9424.
QIN X W, HE J, YU Y, et al. The roles of mandarin fish STING in innate immune defense against infectious spleen and kidney necrosis virus infections. Fish Shellfish Immunol, 2020, 100: 80−89[2021-08-21]. https://doi.org/10.1016/j.fsi.2020.02.062.
VISHNOI A, RANI S. MiRNA biogenesis and regulation of diseases: An overview. Methods Mol Biol, 2017, 1509: 1−10[2021-08-21]. https://doi.org/10.1007/978-1-4939-6524-3_1.
ZHU J, FU H, WU Y, et al. Function of lncRNAs and approaches to lncRNA-protein interactions. Sci China Life Sci,2013,56(10): 876–885.
QU S, YANG X, LI X, et al. Circular RNA: A new star of noncoding RNAs. Cancer Lett,2015,365(2): 141–148.
OZATA D M, GAINETDINOV I, ZOCH A, et al. Piwi-interacting RNAs: Small RNAs with big functions. Nat Rev Genet,2019,20(2): 89–108.
ZHU L, LI J, GONG Y, et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol Cancer, 2019, 18(1): 74[2021-08-21]. https://doi.org/10.1186/s12943-019-1000-8.
PARK J, AHN S H, SHIN M G, et al. TRNA-derived small RNAs: Novel epigenetic regulators. Cancers (Basel), 2020, 12(10): 2773[2021-08-21]. https://doi.org/10.3390/cancers12102773.
THAISS C A, ZMORA N, LEVY M, et al. The microbiome and innate immunity. Nature,2016,535(7610): 65–74.
THAISS C A, LEVY M, ITAV S, et al. Integration of innate immune signaling. Trends Immunol,2016,37(2): 84–101.
VIDYA M K, KUMAR V G, SEJIAN V, et al. Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals. Int Rev Immunol,2018,37(1): 20–36.
MAHARJAN A S, PILLING D, GOMER R H. Toll-like receptor 2 agonists inhibit human fibrocyte differentiation. Fibrogenesis Tissue Repair, 2010, 3: 23[2021-08-21]. https://doi.org/10.1186/1755-1536-3-23.
PARK S R, KIM D J, HAN S H, et al. Diverse toll-like receptors mediate cytokine production by fusobacterium nucleatum and aggregatibacter actinomycetemcomitans in macrophages. Infect Immun,2014,82(5): 1914–1920.
VÁZQUEZ-MENDOZA A, CARRERO J C, RODRIGUEZ-SOSA M. Parasitic infections: A role for C-type lectins receptors. Biomed Res Int, 2013, 2013: 456352[2021-08-21]. https://doi.org/10.1155/2013/456352.
LIU B, GAO C. Regulation of MAVs activation through post-translational modifications. Curr Opin Immunol, 2018, 50: 75−81[2021-08-21]. https://doi.org/10.1016/j.coi.2017.12.002.
CASTANIER C, ZEMIRLI N, PORTIER A, et al. MAVs ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type Ⅰ interferon production after activation of the antiviral RIG-Ⅰ-like receptors. BMC Biol, 2012, 10: 44[2021-08-21]. https://doi.org/ 10.1186/1741-7007-10-44.
GRAY E E, WINSHIP D, SNYDER J M, et al. The AIM2-like receptors are dispensable for the interferon response to intracellular DNA. Immunity,2016,45(2): 255–266.
HORNUNG V, HARTMANN R, ABLASSER A, et al. OAS proteins and cGAS: Unifying concepts in sensing and responding to cytosolic nucleic acids. Nat Rev Immunol,2014,14(8): 521–528.
LI Z, CHEN B, FENG M, et al. MicroRNA-23b promotes avian leukosis virus subgroup j (ALV-j) replication by targeting IRF1. Sci Rep, 2015, 5: 10294[2021-08-21]. https://doi.org/10.1038/srep10294.
LEE Y S, BAO X, LEE H H, et al. Nc886, a novel suppressor of the type Ⅰ interferon response upon pathogen intrusion. Int J Mol Sci, 2021, 22(4): 2003[2021-08-21]. https://doi.org/10.3390/ijms22042003.
TANG Y, LUO X, CUI H, et al. MicroRNA-146a contributes to abnormal activation of the type Ⅰ interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum,2009,60(4): 1065–1075.
ZHENG W, CHU Q, XU T. The long noncoding RNANARL regulates immune responses via microRNA-mediated NOD1 downregulation in teleost fish. J Biol Chem, 2021. 296: 100414[2021-08-21]. https://doi.org/10.1016/j.jbc.2021.100414.
LI X, GUO G, LU M, et al. Long noncoding RNA lnc-MXA inhibits beta interferon transcription by forming RNA-DNA triplexes at its promoter. J Virol, 2019, 93(21): e00786−19[2021-08-21]. https://journals.asm.org/doi/10.1128/JVI.00786-19.
AZNAOUROVA M, JANGA H, SEFRIED S, et al. Noncoding RNA MAIL1 is an integral component of the TLR4-TRIF pathway. Proc Natl Acad Sci U S A,2020,117(16): 9042–9053.
ZHENG W, CHU Q, YANG L, et al. Circular RNA circDtx1 regulates IRF3-mediated antiviral immune responses through suppression of mir-15a-5p-dependent TRIF downregulation in teleost fish. PLoS Pathog, 2021, 17(3): e1009438[2021-08-21]. https://doi.org/10.1371/journal. ppat.1009438.
LIU W, JIN Y, ZHANG W, et al. MiR-202-5p inhibits RIG-Ⅰ-dependent innate immune responses to rgnnv infection by targeting TRIM25 to mediate RIG-Ⅰ ubiquitination. Viruses, 2020, 12(3): 261[2021-08-21]. https://doi.org/10.3390/v12030261.
QIU Y, GENG X, BAN J, et al. MicroRNA-218 inhibits type Ⅰ interferon production and facilitates virus immune evasion via targeting RIG-Ⅰ. Biotechnol Appl Biochem,2020,67(3): 396–403.
NAM R K, BENATAR T, AMEMIYA Y, et al. MiR-139 induces an interferon-β response in prostate cancer cells by binding to RIG-Ⅰ. Cancer Genomics Proteomics,2021,18(3): 197–206.
JIANG M, ZHANG S, YANG Z, et al. Self-recognition of an inducible host lncRNA by RIG-Ⅰ feedback restricts innate immune response. Cell, 2018, 173(4): 906−919.e913[2021-08-21]. https://doi.org/10.1016/j.cell. 2018.03.064.
MA H, HAN P, YE W, et al. The long noncoding RNA NEAT1 exerts anti-hantaviral effects by acting as positive feedback for RIG-Ⅰ signaling. J Virol, 2017, 91(9): e02250−16[2021-08-21]. https://doi.org/10.1128/JVI. 02250-16.
XU T, CHU Q, CUI J, et al. Inducible microRNA-3570 feedback inhibits the RIG-Ⅰ-dependent innate immune response to rhabdovirus in teleost fish by targeting MAVs/IPS-1. J Virol, 2018, 92(2): e01594−17[2021-08-21]. https://doi.org/10.1128/JVI.01594-17.
YASUKAWA K, KINOSHITA D, YAKU K, et al. The microRNAs miR-302b and miR-372 regulate mitochondrial metabolism via the SLC25A12 transporter, which controls MAVs-mediated antiviral innate immunity. J Biol Chem,2020,295(2): 444–457.
CHU Q, XU T, ZHENG W, et al. Long noncoding RNA MARL regulates antiviral responses through suppression miR-122-dependent MAVs downregulation in lower vertebrates. PLoS Pathog, 2020, 16(7): e1008670[2021-08-21]. https://doi.org/10.1371/journal.ppat.1008670.
YU Q, CHU L, LI Y, et al. MiR-23a/b suppress cGAS-mediated innate and autoimmunity. Cell Mol Immunol,2021,18(5): 1235–1248.
WU M Z, CHENG W C, CHEN S F, et al. MiR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS. Nat Cell Biol,2017, 19(10): 1286–1296.
XU T, CHU Q, CUI J. Rhabdovirus-inducible microRNA-210 modulates antiviral innate immune response via targeting STING/MITA in fish. J Immunol,2018,201(3): 982–994.
CHEN J H, FENG D D, CHEN Y F, et al. Long non-coding RNAMALAT1 targeting STING transcription promotes bronchopulmonary dysplasia through regulation of CREB. J Cell Mol Med,2020,24(18): 10478–10492.
NEGISHI H, TANIGUCHI T, YANAI H. The interferon (IFN) class of cytokines and the IFN regulatory factor (IRF) transcription factor family. Cold Spring Harb Perspect Biol, 2018, 10(11): a028423[2021-08-21]. https://doi.org/10.1101/cshperspect.a028423.
ZHANG B C, ZHOU Z J, SUN L. Pol-miR-731, a teleost mirna upregulated by megalocytivirus, negatively regulates virus-induced type Ⅰ interferon response, apoptosis, and cell cycle arrest. Sci Rep, 2016, 6: 28354[2021-08-21]. https://doi.org/10.1038/srep28354.
DAI P, CAO H, MERGHOUB T, et al. Myxoma virus induces type Ⅰ interferon production in murine plasmacytoid dendritic cells via a TLR9/myd88-, IRF5/IRF7-, and IFNAR-dependent pathway. J Virol, 2011,85(20): 10814–10825.
O’NEILL L A, BOWIE A G. The family of five: TIR-domain-containing adaptors in toll-like receptor signalling. Nat Rev Immunol,2007,7(5): 353–364.
Refbacks
- There are currently no refbacks.



