m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00567)
Target Name RIG-I-like receptor 1 (RIG-I)
Synonyms
ATP-dependent RNA helicase DDX58; DEAD box protein 58; RIG-I-like receptor 1; RLR-1; Retinoic acid-inducible gene 1 protein; RIG-1; Retinoic acid-inducible gene I protein; RIG-I
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Gene Name RIG-I
Chromosomal Location 9p21.1
Family Helicase family, RLR subfamily
Function
Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons. Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) . In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) . It also detects rotaviruses and reoviruses . Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.65). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.
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Gene ID 23586
Uniprot ID
DDX58_HUMAN
HGNC ID
HGNC:19102
Ensembl Gene ID
ENSG00000107201
KEGG ID
hsa:23586
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
RIG-I can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: -1.14E+00
p-value: 3.48E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between RIG-I and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 1.75E+00 GSE60213
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Target Regulation Down regulation
Responsed Disease Acute hepatitis B ICD-11: 1E50.1
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Target Regulation Down regulation
Responsed Disease Acute hepatitis C ICD-11: 1E50.2
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary In SARS-CoV-2 infection, depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I-like receptor 1 (RIG-I) binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression.
Target Regulation Down regulation
Responsed Disease COVID-19 ICD-11: RA01
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
Cell Process Immune responses
In-vitro Model Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
Caco-2 Colon adenocarcinoma Homo sapiens CVCL_0025
HEK293-FT Normal Homo sapiens CVCL_6911
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line Embryonic stem cells Mus musculus
Treatment: METTL14 knockout mESCs
Control: Wild type mESCs
 GSE156481
Regulation
logFC: -1.26E+00
p-value: 3.52E-15
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Target Regulation Down regulation
Responsed Disease Acute hepatitis B ICD-11: 1E50.1
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Target Regulation Down regulation
Responsed Disease Acute hepatitis C ICD-11: 1E50.2
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line Cal27 cell line Homo sapiens
Treatment: siALKBH5 Cal27 cells
Control: siScramble Cal27 cells
 GSE185886
Regulation
logFC: 7.29E-01
p-value: 2.91E-02
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary ALKBH5 overexpression inhibits RIG-I-mediated IFN-Alpha secretion through the IKK-Epsilon/TBK1/IRF3 pathway. Upregulation of AKLBH5 negatively correlates with RIG-I-like receptor 1 (RIG-I) and IFN-Alpha expression in head and neck squamous cell carcinoma (HNSCC) patients.
Target Regulation Down regulation
Responsed Disease Head and neck squamous carcinoma ICD-11: 2B6E
 Disease Info 
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
SCC-4 Tongue squamous cell carcinoma Homo sapiens CVCL_1684
SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
HEK293T Normal Homo sapiens CVCL_0063
()
In-vivo Model For the subcutaneous implantation model, 1 × 106 Cal27 cells stably transduced with lentivirus were injected into the left or right flanks of BALB/c nude mice (aged 4-6 weeks). Following stable transfection, 2 × 105 SCC7 cells were subcutaneously inoculated into C3H mice (aged 6-8 weeks).
Acute viral hepatitis [ICD-11: 1E50]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Responsed Disease Acute hepatitis B [ICD-11: 1E50.1]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Responsed Disease Acute hepatitis C [ICD-11: 1E50.2]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 3 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Responsed Disease Acute hepatitis B [ICD-11: 1E50.1]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Experiment 4 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 and METTL14 leads to an increase in viral RNA recognition by RIG-I-like receptor 1 (RIG-I), thereby stimulating type I interferon production. The obvious advantage is that m6A deficiency in HBV and HCV induces a higher IFN synthesis and in turn enhance adaptive immunity.
Responsed Disease Acute hepatitis C [ICD-11: 1E50.2]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Head and neck squamous carcinoma [ICD-11: 2B6E]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary ALKBH5 overexpression inhibits RIG-I-mediated IFN-Alpha secretion through the IKK-Epsilon/TBK1/IRF3 pathway. Upregulation of AKLBH5 negatively correlates with RIG-I-like receptor 1 (RIG-I) and IFN-Alpha expression in head and neck squamous cell carcinoma (HNSCC) patients.
Responsed Disease Head and neck squamous carcinoma [ICD-11: 2B6E]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
In-vitro Model CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
SCC-4 Tongue squamous cell carcinoma Homo sapiens CVCL_1684
SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
HEK293T Normal Homo sapiens CVCL_0063
()
In-vivo Model For the subcutaneous implantation model, 1 × 106 Cal27 cells stably transduced with lentivirus were injected into the left or right flanks of BALB/c nude mice (aged 4-6 weeks). Following stable transfection, 2 × 105 SCC7 cells were subcutaneously inoculated into C3H mice (aged 6-8 weeks).
COVID-19 [ICD-11: RA01]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary In SARS-CoV-2 infection, depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I-like receptor 1 (RIG-I) binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression.
Responsed Disease COVID-19 [ICD-11: RA01]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response RIG-I-like receptor signaling pathway hsa04622
Cell Process Immune responses
In-vitro Model Calu-3 Lung adenocarcinoma Homo sapiens CVCL_0609
Caco-2 Colon adenocarcinoma Homo sapiens CVCL_0025
HEK293-FT Normal Homo sapiens CVCL_6911
References
Ref 1 N (6)-Methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling. J Biol Chem. 2020 Sep 11;295(37):13123-13133. doi: 10.1074/jbc.RA120.014260. Epub 2020 Jul 27.
Ref 2 METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection. Cell Rep. 2021 May 11;35(6):109091. doi: 10.1016/j.celrep.2021.109091. Epub 2021 May 3.
Ref 3 The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKEpsilon/TBK1/IRF3 pathway in head and neck squamous cell carcinoma. Mol Cancer. 2022 Apr 9;21(1):97. doi: 10.1186/s12943-022-01572-2.