Genomes and Genes
Gene Symbol: DDX58
Description: DExD/H-box helicase 58
Alias: RIG-I, RIGI, RLR-1, SGMRT2, DEAD (Asp-Glu-Ala-Asp) box polypeptide 58, DEAD box protein 58, DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide, RNA helicase RIG-I, retinoic acid-inducible gene 1 protein, retinoic acid-inducible gene I protein
- Wang Y, Ludwig J, Schuberth C, Goldeck M, Schlee M, Li H, et al. Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I. Nat Struct Mol Biol. 2010;17:781-7 pubmed publisher....
- Gee P, Chua P, Gevorkyan J, Klumpp K, Najera I, Swinney D, et al. Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity. J Biol Chem. 2008;283:9488-96 pubmed publisher....
- Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004;5:730-7 pubmed..Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes. ..
- Saito T, Hirai R, Loo Y, Owen D, Johnson C, Sinha S, et al. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci U S A. 2007;104:582-7 pubmed..Modulation of RIG-I/LGP2 interaction dynamics may have therapeutic implications for immune regulation. ..
- Rajsbaum R, Albrecht R, Wang M, Maharaj N, Versteeg G, Nistal Villán E, et al. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog. 2012;8:e1003059 pubmed publisher..In conclusion, our results indicate that influenza NS1 protein targets TRIM25 and Riplet ubiquitin E3 ligases in a species-specific manner for the inhibition of RIG-I ubiquitination and antiviral IFN production...
- Kitamura H, Matsuzaki Y, Kimura K, Nakano H, Imaizumi T, Satoh K, et al. Cytokine modulation of retinoic acid-inducible gene-I (RIG-I) expression in human epidermal keratinocytes. J Dermatol Sci. 2007;45:127-34 pubmed..Our results suggest that RIG-I might operate not only as a RNA helicase but also as a mediator of the cytokine network in the inflammatory skin diseases, such as psoriasis vulgaris. ..
- Pothlichet J, Burtey A, Kubarenko A, Caignard G, Solhonne B, Tangy F, et al. Study of human RIG-I polymorphisms identifies two variants with an opposite impact on the antiviral immune response. PLoS ONE. 2009;4:e7582 pubmed publisher..This work also demonstrated that serine 183 is a residue that critically regulates RIG-I-induced antiviral signaling. ..
- Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, et al. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest. 2009;119:2399-411 pubmed publisher..Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis. ..
- Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald K, Hornung V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol. 2009;10:1065-72 pubmed publisher..This pathway was important in the sensing of Epstein-Barr virus-encoded small RNAs, which were transcribed by RNA polymerase III and then triggered RIG-I activation. Thus, RNA polymerase III and RIG-I are pivotal in sensing viral DNA. ..
- Gack M, Albrecht R, Urano T, Inn K, Huang I, Carnero E, et al. Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe. 2009;5:439-49 pubmed publisher..Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses. ..
- Luo D, Ding S, Vela A, Kohlway A, Lindenbach B, Pyle A. Structural insights into RNA recognition by RIG-I. Cell. 2011;147:409-22 pubmed publisher....
- Ablasser A, Poeck H, Anz D, Berger M, Schlee M, Kim S, et al. Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes. J Immunol. 2009;182:6824-33 pubmed publisher....
- Schmidt A, Schwerd T, Hamm W, Hellmuth J, Cui S, Wenzel M, et al. 5'-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. Proc Natl Acad Sci U S A. 2009;106:12067-72 pubmed publisher..Together, our findings accurately define a minimal molecular pattern sufficient to activate RIG-I that can be found in viral genomes or transcripts. ..
- Bamming D, Horvath C. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. J Biol Chem. 2009;284:9700-12 pubmed publisher..In addition, neither enzymatic activity nor RNA binding was required for negative regulation of antiviral signaling by LGP2, supporting an RNA-independent interference mechanism. ..
- Kowalinski E, Lunardi T, McCarthy A, Louber J, Brunel J, Grigorov B, et al. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell. 2011;147:423-35 pubmed publisher..These findings significantly advance our molecular understanding of the activation of innate immune signaling helicases. ..
- Cheng G, Zhong J, Chisari F. Inhibition of dsRNA-induced signaling in hepatitis C virus-infected cells by NS3 protease-dependent and -independent mechanisms. Proc Natl Acad Sci U S A. 2006;103:8499-504 pubmed..The results also suggest that HCV blocks the synthetic dsRNA-induced signaling pathway at a point upstream of MAVS/IPS-1, and that it does so by an NS3-independent mechanism. ..
- Gao D, Yang Y, Wang R, Zhou X, Diao F, Li M, et al. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PLoS ONE. 2009;4:e5760 pubmed publisher..These findings suggest that REUL is an E3 ubiquitin ligase of RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity. ..
- Chiu Y, Macmillan J, Chen Z. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138:576-91 pubmed publisher..These results suggest that RNA Pol-III is a cytosolic DNA sensor involved in innate immune responses. ..
- Li S, Zheng H, Mao A, Zhong B, Li Y, Liu Y, et al. Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J Biol Chem. 2010;285:4291-7 pubmed publisher..These findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6. ..
- Feng M, Ding Z, Xu L, Kong L, Wang W, Jiao S, et al. Structural and biochemical studies of RIG-I antiviral signaling. Protein Cell. 2013;4:142-54 pubmed publisher..These findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS. ..
- Zhao C, Denison C, Huibregtse J, Gygi S, Krug R. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A. 2005;102:10200-5 pubmed..By targeting a wide array of constitutively expressed proteins, ISG15 conjugation greatly extends the repertoire of cellular functions that are affected by IFN-alpha/beta. ..
- Pichlmair A, Schulz O, Tan C, Näslund T, Liljestrom P, Weber F, et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science. 2006;314:997-1001 pubmed....
- Xu L, Wang Y, Han K, Li L, Zhai Z, Shu H. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19:727-40 pubmed..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling. ..
- Civril F, Bennett M, Moldt M, Deimling T, Witte G, Schiesser S, et al. The RIG-I ATPase domain structure reveals insights into ATP-dependent antiviral signalling. EMBO Rep. 2011;12:1127-34 pubmed publisher..Overall, our results indicate that the activation of RIG-I occurs through an RNA- and ATP-driven structural switch in the SF2 domain. ..
- Hirata Y, Broquet A, Menchén L, Kagnoff M. Activation of innate immune defense mechanisms by signaling through RIG-I/IPS-1 in intestinal epithelial cells. J Immunol. 2007;179:5425-32 pubmed..Virus replication and virus-induced cell death increased in IECs in which RIG-I was silenced, consistent with the importance of the RIG-I signaling pathway in IEC antiviral innate immune defense mechanisms. ..
- Rehwinkel J, Tan C, Goubau D, Schulz O, Pichlmair A, Bier K, et al. RIG-I detects viral genomic RNA during negative-strand RNA virus infection. Cell. 2010;140:397-408 pubmed publisher..Rather, single-stranded RNA viral genomes bearing 5'-triphosphates constitute the natural RIG-I agonists that trigger cell-intrinsic innate immune responses during infection. ..
- Jiang F, Ramanathan A, Miller M, Tang G, Gale M, Patel S, et al. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature. 2011;479:423-7 pubmed publisherRetinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs...
- Baum A, Sachidanandam R, Garcia Sastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc Natl Acad Sci U S A. 2010;107:16303-8 pubmed publisher..Our analysis for the first time identifies RIG-I PAMPs under natural infection conditions and implies that full-length genomes of single segmented RNA virus families are not bound by RIG-I during infection. ..
- Hagmann C, Herzner A, Abdullah Z, Zillinger T, Jakobs C, Schuberth C, et al. RIG-I detects triphosphorylated RNA of Listeria monocytogenes during infection in non-immune cells. PLoS ONE. 2013;8:e62872 pubmed publisher..Our results show that detection of Listeria RNA by RIG-I represents a non-redundant cytosolic immunorecognition pathway in non-immune cells lacking a functional STING dependent signaling pathway. ..
- Chen Z, Benureau Y, Rijnbrand R, Yi J, Wang T, Warter L, et al. GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. J Virol. 2007;81:964-76 pubmed publisher..These data provide further support for the use of GBV-B infection in small primates as an accurate surrogate model for deciphering virus-host interactions in hepacivirus pathogenesis...
- Ovsyannikova I, Haralambieva I, Dhiman N, O Byrne M, Pankratz V, Jacobson R, et al. Polymorphisms in the vitamin A receptor and innate immunity genes influence the antibody response to rubella vaccination. J Infect Dis. 2010;201:207-13 pubmed publisher..016) after having been previously found to play a significant functional role. These findings further expand our immunogenetic understanding of mechanisms of rubella vaccine-induced immunity. ..
- Morosky S, Zhu J, Mukherjee A, Sarkar S, Coyne C. Retinoic acid-induced gene-I (RIG-I) associates with nucleotide-binding oligomerization domain-2 (NOD2) to negatively regulate inflammatory signaling. J Biol Chem. 2011;286:28574-83 pubmed publisher....
- Xia Z, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, et al. Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 2009;461:114-9 pubmed publisher..These results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation. ..
- Sumpter R, Loo Y, Foy E, Li K, Yoneyama M, Fujita T, et al. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol. 2005;79:2689-99 pubmed..RIG-I is thus a pathogen receptor that regulates cellular permissiveness to HCV replication and, as an interferon-responsive gene, may play a key role in interferon-based therapies for the treatment of HCV infection. ..
- Su Z, Sarkar D, Emdad L, Barral P, Fisher P. Central role of interferon regulatory factor-1 (IRF-1) in controlling retinoic acid inducible gene-I (RIG-I) expression. J Cell Physiol. 2007;213:502-10 pubmed..IRF-1 is a tumor suppressor and the expression profile of RIG-I together with its regulation by IRF-1 and the presence of a caspase-recruitment domain in RIG-I suggest that RIG-I might also possess tumor suppressor properties. ..
- Gack M, Nistal Villán E, Inn K, Garcia Sastre A, Jung J. Phosphorylation-mediated negative regulation of RIG-I antiviral activity. J Virol. 2010;84:3220-9 pubmed publisher..While Thr-170 phosphorylation keeps RIG-I latent, Lys-172 ubiquitination enables RIG-I to form a stable complex with MAVS, thereby inducing IFN signal transduction. ..
- Seth R, Sun L, Ea C, Chen Z. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122:669-82 pubmed..The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity...
- ..Understanding the processes of RLR signaling and response will provide insights to guide RLR-targeted therapeutics for antiviral and immune-modifying applications. ..
- Marr N, Wang T, Kam S, Hu Y, Sharma A, Lam A, et al. Attenuation of respiratory syncytial virus-induced and RIG-I-dependent type I IFN responses in human neonates and very young children. J Immunol. 2014;192:948-57 pubmed publisher..Our results suggest that human pDCs are less functional in early life, which may contribute to the increased susceptibility of infants and young children to severe RSV disease. ..
- Vela A, Fedorova O, Ding S, Pyle A. The thermodynamic basis for viral RNA detection by the RIG-I innate immune sensor. J Biol Chem. 2012;287:42564-73 pubmed publisher..Covalent linkage between the domains enhances RNA ligand specificity while reducing overall binding affinity, thereby providing a mechanism for discriminating virus from host RNA. ..
- Ferrage F, Dutta K, Nistal Villán E, Patel J, Sanchez Aparicio M, De Ioannes P, et al. Structure and dynamics of the second CARD of human RIG-I provide mechanistic insights into regulation of RIG-I activation. Structure. 2012;20:2048-61 pubmed publisher..Collectively, our data suggests a close interplay between phosphorylation, ubiquitination, and activation of human RIG-I, all mediated by CARD2. ..
- Peisley A, Wu B, Xu H, Chen Z, Hur S. Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature. 2014;509:110-4 pubmed publisher..Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes...
- Cui S, Eisenächer K, Kirchhofer A, Brzózka K, Lammens A, Lammens K, et al. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. Mol Cell. 2008;29:169-79 pubmed publisher..Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity. ..
- Loo Y, Owen D, Li K, Erickson A, Johnson C, Fish P, et al. Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. Proc Natl Acad Sci U S A. 2006;103:6001-6 pubmed..HCV protease inhibitors effectively prevent IPS-1 proteolysis, suggesting they may be capable of restoring this innate host response in clinical practice. ..
- Kageyama M, Takahasi K, Narita R, Hirai R, Yoneyama M, Kato H, et al. 55 Amino acid linker between helicase and carboxyl terminal domains of RIG-I functions as a critical repression domain and determines inter-domain conformation. Biochem Biophys Res Commun. 2011;415:75-81 pubmed publisher..These findings shed light on the structural regulation of RIG-I function. ..
- Guo Z, Chen L, Zeng H, Gomez J, Plowden J, Fujita T, et al. NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I. Am J Respir Cell Mol Biol. 2007;36:263-9 pubmed..These results provide further information on the mechanism by which IAV NS1 antagonizes the host antiviral response. ..
- Atencia R, Bustamante F, Valdivieso A, Arrieta A, Riñón M, Prada A, et al. Differential expression of viral PAMP receptors mRNA in peripheral blood of patients with chronic hepatitis C infection. BMC Infect Dis. 2007;7:136 pubmed....
- Huang C, Kolokoltsova O, Yun N, Seregin A, Poussard A, Walker A, et al. Junín virus infection activates the type I interferon pathway in a RIG-I-dependent manner. PLoS Negl Trop Dis. 2012;6:e1659 pubmed publisher....
- Nasirudeen A, Wong H, Thien P, Xu S, Lam K, Liu D. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis. 2011;5:e926 pubmed publisher..Collectively, our studies demonstrate that the intracellular RNA virus sensors (RIG-I, MDA5 and TLR3) are activated upon DV infection and are essential for host defense against the virus. ..
- Schlee M, Roth A, Hornung V, Hagmann C, Wimmenauer V, Barchet W, et al. Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity. 2009;31:25-34 pubmed publisher....
- Solis M, Nakhaei P, Jalalirad M, Lacoste J, Douville R, Arguello M, et al. RIG-I-mediated antiviral signaling is inhibited in HIV-1 infection by a protease-mediated sequestration of RIG-I. J Virol. 2011;85:1224-36 pubmed publisher..This study reveals a novel PR-dependent mechanism employed by HIV-1 to counteract the early IFN response to viral RNA in infected cells. ..
- Marq J, Kolakofsky D, Garcin D. Unpaired 5' ppp-nucleotides, as found in arenavirus double-stranded RNA panhandles, are not recognized by RIG-I. J Biol Chem. 2010;285:18208-16 pubmed publisher..The presence of this unpaired 5' ppp-nucleotide is thus another way that some viruses appear to use to avoid detection by cytoplasmic pattern recognition receptors...
- Barral P, Sarkar D, Su Z, Barber G, DeSalle R, Racaniello V, et al. Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: key regulators of innate immunity. Pharmacol Ther. 2009;124:219-34 pubmed publisher..We also consider the function of these cytoplasmic sensors in apoptosis, development and differentiation, and diabetes. ..
- Hu J, Nistal Villán E, Voho A, Ganee A, Kumar M, Ding Y, et al. A common polymorphism in the caspase recruitment domain of RIG-I modifies the innate immune response of human dendritic cells. J Immunol. 2010;185:424-32 pubmed publisher..to the induction of the IFNbeta gene, IFNB1, through the activation of the RNA helicase RIG-I, which is encoded by DDX58. Expression levels of IFNB1 and DDX58 in infected DCs showed positive correlations at the population and the ..
- Lin R, Yang L, Nakhaei P, Sun Q, Sharif Askari E, Julkunen I, et al. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J Biol Chem. 2006;281:2095-103 pubmed..These results suggest that the virus-inducible, NF-kappaB-dependent activation of A20 functions as a negative regulator of RIG-I-mediated induction of the antiviral state. ..
- Cui J, Song Y, Li Y, Zhu Q, Tan P, Qin Y, et al. USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors. Cell Res. 2014;24:400-16 pubmed publisher..Our findings identify a previously unrecognized role of USP3 in RIG-I activation and provide insights into the mechanisms by which USP3 inhibits RIG-I signaling and antiviral immunity. ..
- Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell. 2010;141:315-30 pubmed publisher..Our results delineate the mechanism of RIG-I activation, identify CARD domains as a ubiquitin sensor, and demonstrate that unanchored K63-polyubiquitin chains are signaling molecules in antiviral innate immunity...
- Hrincius E, Dierkes R, Anhlan D, Wixler V, Ludwig S, Ehrhardt C. Phosphatidylinositol-3-kinase (PI3K) is activated by influenza virus vRNA via the pathogen pattern receptor Rig-I to promote efficient type I interferon production. Cell Microbiol. 2011;13:1907-19 pubmed publisher..These data identify PI3K as factor that is activated as part of the Rig-I mediated anti-pathogen response to enhance expression of type I interferons. ..
- Barral P, Sarkar D, Fisher P, Racaniello V. RIG-I is cleaved during picornavirus infection. Virology. 2009;391:171-6 pubmed publisher..Rather, the viral proteinase 3C(pro) cleaves RIG-I, both in vitro and in cells. Cleavage of RIG-I during picornavirus infection may constitute another mechanism for attenuating the innate response to viral infection. ..
- Fan L, Briese T, Lipkin W. Z proteins of New World arenaviruses bind RIG-I and interfere with type I interferon induction. J Virol. 2010;84:1785-91 pubmed publisher....
- Dixit E, Kagan J. Intracellular pathogen detection by RIG-I-like receptors. Adv Immunol. 2013;117:99-125 pubmed publisher..RLR signaling requires the adapter protein MAVS to induce type I interferon, interferon-stimulated genes, and proinflammatory cytokines. This review focuses on the molecular and cell biological requirements for RLR signal transduction. ..