RIG-I

DEAD (Asp-Glu-Ala-Asp) box polypeptide 58
Rendering based on PDB 2QFB​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LWD​, 2LWE​, 2QFB​, 2QFD​, 2RMJ​, 2YKG​, 3LRN​, 3LRR​, 3NCU​, 3OG8​, 3TMI​, 3ZD6​, 3ZD7​, 4AY2​, 4BPB​, 4NQK​, 4ON9​, 4P4H​
Identifiers
Symbols	DDX58 ; RIG-I; RIGI; RLR-1; SGMRT2
External IDs	OMIM: 609631 MGI: 2442858 HomoloGene: 32215 GeneCards: DDX58 Gene
EC number	3.6.4.13
Gene ontology Molecular function • double-stranded DNA binding • double-stranded RNA binding • single-stranded RNA binding • helicase activity • protein binding • ATP binding • zinc ion binding • identical protein binding Cellular component • cytoplasm • cytosol • bicellular tight junction • actin cytoskeleton • ruffle membrane Biological process • positive regulation of defense response to virus by host • metabolic process • detection of virus • response to virus • positive regulation of gene expression • viral process • regulation of cell migration • negative regulation of type I interferon production • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of interferon-alpha production • positive regulation of interferon-beta production • positive regulation of interleukin-6 production • positive regulation of interleukin-8 production • regulation of type III interferon production • cytoplasmic pattern recognition receptor signaling pathway in response to virus • RIG-I signaling pathway • positive regulation of transcription factor import into nucleus • response to exogenous dsRNA • innate immune response • positive regulation of transcription from RNA polymerase II promoter • positive regulation of sequence-specific DNA binding transcription factor activity 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	NP_766277
Location (UCSC)	Chr 9: 32.46 – 32.53 Mb	Chr 4: 40.2 – 40.24 Mb
PubMed search

RIG-I (retinoic acid-inducible gene 1) 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.^[1] RIG-I typically recognizes short (< 4000nt) 5′ triphosphate uncapped double stranded or single stranded RNA.^[2][3][4] RIG-I and MDA5 are involved in activating MAVS and triggering an antiviral response.^[5] 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.^[6]

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.^[7]

References

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. "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.