RIG-I

DDX58
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LWD, 2LWE, 2QFB, 2QFD, 2RMJ, 2YKG, 3LRN, 3LRR, 3NCU, 3OG8, 3ZD6, 3ZD7, 4AY2, 4BPB, 4NQK, 4ON9, 4P4H, 5E3H, 5F98, 5F9F, 5F9H
Identifiers
Aliases	DDX58, DEAD (Asp-Glu-Ala-Asp) box polypeptide 58, RIGI, RLR-1, SGMRT2, RIG-I, DEXD/H-box helicase 58
External IDs	MGI: 2442858 HomoloGene: 32215 GeneCards: DDX58
Gene ontology Molecular function • nucleotide binding • helicase activity • zinc ion binding • metal ion binding • hydrolase activity, acting on acid anhydrides • protein binding • single-stranded RNA binding • identical protein binding • RNA binding • double-stranded RNA binding • double-stranded DNA binding • hydrolase activity • ATP binding • nucleic acid binding Cellular component • cytoplasm • cytosol • cell projection • membrane • bicellular tight junction • plasma membrane • ruffle membrane • cell junction • actin cytoskeleton • cytoskeleton Biological process • regulation of cell migration • response to exogenous dsRNA • positive regulation of interferon-alpha production • immune system process • response to virus • positive regulation of sequence-specific DNA binding transcription factor activity • positive regulation of transcription factor import into nucleus • cytoplasmic pattern recognition receptor signaling pathway in response to virus • positive regulation of gene expression • positive regulation of granulocyte macrophage colony-stimulating factor production • defense response to virus • positive regulation of interleukin-8 production • positive regulation of interleukin-6 production • negative regulation of type I interferon production • detection of virus • viral process • innate immune response • positive regulation of transcription from RNA polymerase II promoter • RIG-I signaling pathway • regulation of type III interferon production • positive regulation of defense response to virus by host • positive regulation of interferon-beta production Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23586	230073
Ensembl	ENSG00000107201	ENSMUSG00000040296
UniProt	O95786	Q6Q899
RefSeq (mRNA)	NM_014314	NM_172689
RefSeq (protein)	NP_055129.2	NP_766277.3
Location (UCSC)	Chr 9: 32.46 – 32.53 Mb	Chr 4: 40.2 – 40.24 Mb
PubMed search	[1]	[2]
Wikidata

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RIG-I (retinoic acid-inducible gene I) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded (in humans) by the DDX58 gene. RIG-I is part of the RIG-I-like receptor family, which also includes MDA5 and LGP2, and functions as a pattern recognition receptor that is a sensor for viruses such as influenza A, Sendai virus, and flavivirus. Certain retroviruses, such as HIV-1, encode a protease that directs RIG-1 to the lysosome for degradation, and thereby evade RIG-1 mediated signaling.^[3] RIG-I typically recognizes short (< 4000nt) 5′ triphosphate uncapped double stranded or single stranded RNA.^[4][5][6] RIG-I and MDA5 are involved in activating MAVS and triggering an antiviral response.^[7] RIG-I is also able to detect non-self 5′-triphosphorylated dsRNA transcribed from AT-rich dsDNA by DNA-dependent RNA polymerase III (Pol III). For many viruses, effective RIG-I-mediated antiviral responses are dependent on functionally active LGP2.^[8]

Function

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular processes involving RNA binding and alteration of RNA secondary structure. RIG-I contains a RNA helicase-DEAD box motifs and a caspase recruitment domain (CARD). RIG-I is involved in viral double-stranded (ds) RNA recognition and the regulation of immune response.^[9]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Solis M, Nakhaei P, Jalalirad M, Lacoste J, Douville R, Arguello M, Zhao T, Laughrea M, Wainberg MA, Hiscott J (Feb 2011). "RIG-I-mediated antiviral signaling is inhibited in HIV-1 infection by a protease-mediated sequestration of RIG-I". Journal of Virology. 85 (3): 1224–36. doi:10.1128/JVI.01635-10. PMC 3020501. PMID 21084468.
4. Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P, Weber F, Reis e Sousa C (Nov 2006). "RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates". Science. 314 (5801): 997–1001. doi:10.1126/science.1132998. PMID 17038589.
5. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (Jul 2004). "The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses". Nature Immunology. 5 (7): 730–7. doi:10.1038/ni1087. PMID 15208624.
6. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S (Jul 2008). "Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5". The Journal of Experimental Medicine. 205 (7): 1601–10. doi:10.1084/jem.20080091. PMC 2442638. PMID 18591409.
7. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ (Aug 2011). "MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response". Cell. 146 (3): 448–61. doi:10.1016/j.cell.2011.06.041. PMC 3179916. PMID 21782231.
8. Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O (Jan 2010). "LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses". Proceedings of the National Academy of Sciences of the United States of America. 107 (4): 1512–7. doi:10.1073/pnas.0912986107. PMC 2824407. PMID 20080593.
9. "Entrez Gene: DDX58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58".

Further reading

• Bowie AG, Fitzgerald KA (Apr 2007). "RIG-I: tri-ing to discriminate between self and non-self RNA". Trends in Immunology. 28 (4): 147–50. doi:10.1016/j.it.2007.02.002. PMID 17307033.
• Imaizumi T, Aratani S, Nakajima T, Carlson M, Matsumiya T, Tanji K, Ookawa K, Yoshida H, Tsuchida S, McIntyre TM, Prescott SM, Zimmerman GA, Satoh K (Mar 2002). "Retinoic acid-inducible gene-I is induced in endothelial cells by LPS and regulates expression of COX-2". Biochemical and Biophysical Research Communications. 292 (1): 274–9. doi:10.1006/bbrc.2002.6650. PMID 11890704.
• Cui XF, Imaizumi T, Yoshida H, Borden EC, Satoh K (Jun 2004). "Retinoic acid-inducible gene-I is induced by interferon-gamma and regulates the expression of interferon-gamma stimulated gene 15 in MCF-7 cells". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 82 (3): 401–5. doi:10.1139/o04-041. PMID 15181474.
• Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (Jul 2004). "The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses". Nature Immunology. 5 (7): 730–7. doi:10.1038/ni1087. PMID 15208624.
• Imaizumi T, Yagihashi N, Hatakeyama M, Yamashita K, Ishikawa A, Taima K, Yoshida H, Inoue I, Fujita T, Yagihashi S, Satoh K (Jul 2004). "Expression of retinoic acid-inducible gene-I in vascular smooth muscle cells stimulated with interferon-gamma". Life Sciences. 75 (10): 1171–80. doi:10.1016/j.lfs.2004.01.030. PMID 15219805.
• Imaizumi T, Yagihashi N, Hatakeyama M, Yamashita K, Ishikawa A, Taima K, Yoshida H, Yagihashi S, Satoh K (Aug 2004). "Upregulation of retinoic acid-inducible gene-I in T24 urinary bladder carcinoma cells stimulated with interferon-gamma". The Tohoku Journal of Experimental Medicine. 203 (4): 313–8. doi:10.1620/tjem.203.313. PMID 15297736.
• Imaizumi T, Hatakeyama M, Yamashita K, Yoshida H, Ishikawa A, Taima K, Satoh K, Mori F, Wakabayashi K (2004). "Interferon-gamma induces retinoic acid-inducible gene-I in endothelial cells". Endothelium. 11 (3-4): 169–73. doi:10.1080/10623320490512156. PMID 15370293.
• Sakaki H, Imaizumi T, Matsumiya T, Kusumi A, Nakagawa H, Kubota K, Nishi N, Nakamura T, Hirashima M, Satoh K, Kimura H (Feb 2005). "Retinoic acid-inducible gene-I is induced by interleukin-1beta in cultured human gingival fibroblasts". Oral Microbiology and Immunology. 20 (1): 47–50. doi:10.1111/j.1399-302X.2005.00181.x. PMID 15612946.
• Sumpter R, Loo YM, Foy E, Li K, Yoneyama M, Fujita T, Lemon SM, Gale M (Mar 2005). "Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I". Journal of Virology. 79 (5): 2689–99. doi:10.1128/JVI.79.5.2689-2699.2005. PMC 548482. PMID 15708988.
• Li K, Chen Z, Kato N, Gale M, Lemon SM (Apr 2005). "Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes". The Journal of Biological Chemistry. 280 (17): 16739–47. doi:10.1074/jbc.M414139200. PMID 15737993.
• Breiman A, Grandvaux N, Lin R, Ottone C, Akira S, Yoneyama M, Fujita T, Hiscott J, Meurs EF (Apr 2005). "Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon". Journal of Virology. 79 (7): 3969–78. doi:10.1128/JVI.79.7.3969-3978.2005. PMC 1061556. PMID 15767399.
• Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM (Jul 2005). "Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways". Proceedings of the National Academy of Sciences of the United States of America. 102 (29): 10200–5. doi:10.1073/pnas.0504754102. PMC 1177427. PMID 16009940.
• Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M, Akira S, Yonehara S, Kato A, Fujita T (Sep 2005). "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity". Journal of Immunology. 175 (5): 2851–8. doi:10.4049/jimmunol.175.5.2851. PMID 16116171.
• Seth RB, Sun L, Ea CK, Chen ZJ (Sep 2005). "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3". Cell. 122 (5): 669–82. doi:10.1016/j.cell.2005.08.012. PMID 16125763.
• Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (Oct 2005). "IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction". Nature Immunology. 6 (10): 981–8. doi:10.1038/ni1243. PMID 16127453.
• Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB (Sep 2005). "VISA is an adapter protein required for virus-triggered IFN-beta signaling". Molecular Cell. 19 (6): 727–40. doi:10.1016/j.molcel.2005.08.014. PMID 16153868.
• Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (Oct 2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus". Nature. 437 (7062): 1167–72. doi:10.1038/nature04193. PMID 16177806.