dead box protein 58


Summary: A DEAD-box RNA helicase that contains an N-terminal DEATH-LIKE DOMAIN, AAA+ ATPase domain, and C-terminal RNA HELICASE activity. It functions as an innate immune receptor through its recognition of viral nucleic acids. It also induces the expression of INTERFERON TYPE I and proinflammatory CYTOKINES. Its ligands include: 5'-triphosphorylated SINGLE-STRANDED RNA, DOUBLE-STRANDED RNA (dsRNA), and short dsRNA (less than 1 kb in length).

Top Publications

  1. Hu M, Liao C, Yang Q, Xie X, Shu H. Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5. J Exp Med. 2017;214:973-989 pubmed publisher
    ..These findings suggest that dynamic sumoylation and desumoylation of MDA5 and RIG-I modulate efficient innate immunity to RNA virus and its timely termination. ..
  2. Lässig C, Hopfner K. Discrimination of cytosolic self and non-self RNA by RIG-I-like receptors. J Biol Chem. 2017;292:9000-9009 pubmed publisher
    ..We specifically focus upon recent findings on the function of the helicase domain in discriminating between different RNAs, and whose malfunctioning causes serious autoimmune diseases. ..
  3. Tan P, He L, Cui J, Qian C, Cao X, Lin M, et al. Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling. Mol Cell. 2017;68:293-307.e5 pubmed publisher
    ..Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity...
  4. Suthar M, Aguirre S, Fernandez Sesma A. Innate immune sensing of flaviviruses. PLoS Pathog. 2013;9:e1003541 pubmed publisher
  5. Baird J, Monjazeb A, Shah O, McGee H, Murphy W, Crittenden M, et al. Stimulating Innate Immunity to Enhance Radiation Therapy-Induced Tumor Control. Int J Radiat Oncol Biol Phys. 2017;99:362-373 pubmed publisher
    ..This review focuses on efforts to combine innate immune stimuli as adjuvants with radiation, creating a distinct and complementary approach from T cell-targeted therapies to enhance antitumor immunity. ..
  6. Nabet B, Qiu Y, Shabason J, Wu T, Yoon T, Kim B, et al. Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer. Cell. 2017;170:352-366.e13 pubmed publisher
    ..Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer. VIDEO ABSTRACT. ..
  7. Mills E, Kelly B, O Neill L. Mitochondria are the powerhouses of immunity. Nat Immunol. 2017;18:488-498 pubmed publisher
    ..These discoveries are revealing mitochondrial targets that could potentially be exploited for therapeutic gain in inflammation and cancer. ..
  8. Yang H, Guo H, Li X, Lin J, Zhang W, Zhao J, et al. Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance. J Immunol. 2017;199:119-128 pubmed publisher
    ..Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance. ..
  9. Narita R, Fujita T. [Nonself RNA-sensing mechanism of RIG-I]. Tanpakushitsu Kakusan Koso. 2008;53:1832-40 pubmed

More Information


  1. Chhabra P, Ranjan P, Cromeans T, Sambhara S, Vinje J. Critical role of RIG-I and MDA5 in early and late stages of Tulane virus infection. J Gen Virol. 2017;98:1016-1026 pubmed publisher
    ..05), suggesting that RIG-I and MDA5 ligands could be used to develop novel preventive and therapeutic measures against norovirus. ..
  2. Blumer T, Coto Llerena M, Duong F, Heim M. SOCS1 is an inducible negative regulator of interferon λ (IFN-λ)-induced gene expression in vivo. J Biol Chem. 2017;292:17928-17938 pubmed publisher
    ..We found that IFN-α signaling is transient and becomes refractory after hours, whereas IFN-λ provides a long-lasting IFN-stimulated gene induction. ..
  3. Youssef S, Hamdy N. SOCS1 and pattern recognition receptors: TLR9 and RIG-I; novel haplotype associations in Egyptian fibrotic/cirrhotic patients with HCV genotype 4. Arch Virol. 2017;162:3347-3354 pubmed publisher
    ..Therefore, performing this specific SNP testing may be of value for the stratification of the population at risk. ..
  4. Ilyushina N, Lugovtsev V, Samsonova A, Sheikh F, Bovin N, Donnelly R. Generation and characterization of interferon-lambda 1-resistant H1N1 influenza A viruses. PLoS ONE. 2017;12:e0181999 pubmed publisher
    ..Our findings demonstrate that influenza viruses can develop increased resistance to the antiviral activity of type III interferons. ..
  5. Sánchez Aparicio M, Garcin D, Rice C, Kolakofsky D, Garcia Sastre A, Baum A. Loss of Sendai virus C protein leads to accumulation of RIG-I immunostimulatory defective interfering RNA. J Gen Virol. 2017;98:1282-1293 pubmed publisher
    ..Our findings indicate that limiting DI genome production is an important function of viral IFN antagonist proteins. ..
  6. Sprokholt J, Kaptein T, van Hamme J, Overmars R, Gringhuis S, Geijtenbeek T. RIG-I-like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune Activation and TH1 Differentiation. J Immunol. 2017;198:4764-4771 pubmed publisher
    ..Therefore, we identified RIG-I and MDA5 as critical players in innate and adaptive immune responses against DENV, and targeting these receptors has the potential to decrease hemorrhagic fever in patients. ..
  7. Ding Z, An K, Xie L, Wu W, Zhang R, Wang D, et al. Transmissible gastroenteritis virus infection induces NF-?B activation through RLR-mediated signaling. Virology. 2017;507:170-178 pubmed publisher
    ..Furthermore, TGEV infection significantly upregulated mRNA expression of RIG-I and MDA5. Taken together, our results indicate that the RLR signaling pathway is involved in TGEV-induced inflammatory responses. ..
  8. Fischer J, Bscheider M, Eisenkolb G, Lin C, Wintges A, Otten V, et al. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci Transl Med. 2017;9: pubmed publisher
    ..Targeting these pathways may help to prevent acute intestinal injury and GVHD during allogeneic transplantation. ..
  9. Spalluto C, Singhania A, Cellura D, Woelk C, Sanchez Elsner T, Staples K, et al. IFN-γ Influences Epithelial Antiviral Responses via Histone Methylation of the RIG-I Promoter. Am J Respir Cell Mol Biol. 2017;57:428-438 pubmed publisher
    ..Further clinical validation is required to determine whether this effect in early life leads to changes in antiviral responses associated with asthma. ..
  10. Zhu H, Lou F, Yin Q, Gao Y, Sun Y, Bai J, et al. RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease. EMBO Mol Med. 2017;9:589-604 pubmed publisher
    ..Thus, our data suggest that the dysregulation in the antiviral immune responses of hosts through the innate pattern recognition receptors may trigger the skin inflammatory conditions in the pathophysiology of psoriasis. ..
  11. Ori D, Murase M, Kawai T. Cytosolic nucleic acid sensors and innate immune regulation. Int Rev Immunol. 2017;36:74-88 pubmed publisher
    ..In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors...
  12. Sayed N, Ospino F, Himmati F, Lee J, Chanda P, Mocarski E, et al. Retinoic Acid Inducible Gene 1 Protein (RIG1)-Like Receptor Pathway Is Required for Efficient Nuclear Reprogramming. Stem Cells. 2017;35:1197-1207 pubmed publisher
    ..To conclude, innate immune signaling mediated by RLR plays a critical role in nuclear reprogramming. Manipulation of innate immune signaling may facilitate nuclear reprogramming to achieve pluripotency. Stem Cells 2017;35:1197-1207. ..
  13. Moresco E, Beutler B. LGP2: positive about viral sensing. Proc Natl Acad Sci U S A. 2010;107:1261-2 pubmed publisher
  14. Jin S, Tian S, Luo M, Xie W, Liu T, Duan T, et al. Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells. Mol Cell. 2017;68:308-322.e4 pubmed publisher
  15. Nguyen T, Smith B, Tate M, Belz G, Barrios M, Elgass K, et al. SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition. Immunity. 2017;47:498-509.e6 pubmed publisher
    ..Thus, SIDT2 has retained the dsRNA transport activity of its C. elegans ortholog, and this transport is important for antiviral immunity. ..
  16. Bowen J, Quicke K, Maddur M, O Neal J, McDonald C, Fedorova N, et al. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells. PLoS Pathog. 2017;13:e1006164 pubmed publisher
  17. Xu L, Wang W, Li Y, Zhou X, Yin Y, Wang Y, et al. RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production. Hepatology. 2017;65:1823-1839 pubmed publisher
    ..Hepatology 2017;65:1823-1839). ..
  18. Wu X, Yang J, Na T, Zhang K, Davidoff A, Yuan B, et al. RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA. PLoS ONE. 2017;12:e0182961 pubmed publisher
    ..Interestingly, the STING protein is not significantly affected by dsDNA in non-HDC HEK293 cells. Our study thus has identified a novel signaling pathway for regulating STING in HDCs. ..
  19. Zhang H, Ye H, Liu S, Deng C, Li X, Shi P, et al. West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5. J Virol. 2017;91: pubmed publisher
    ..The novel findings may guide us to discover new therapeutic targets and develop effective vaccines for WNV infections. ..
  20. Glasner A, Oiknine Djian E, Weisblum Y, Diab M, Panet A, Wolf D, et al. Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules. J Virol. 2017;91: pubmed publisher
    ..Countering MHC class I upregulation and boosting NK cell activity may be employed as prophylactic measures to combat Zika virus infection. ..
  21. Quicke K, Diamond M, Suthar M. Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol. 2017;47:615-628 pubmed publisher
    ..This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG-I, MDA5 and MAVS signaling function...
  22. Chen Y, Kim M, Chen X, Batista P, Aoyama S, Wilusz J, et al. Sensing Self and Foreign Circular RNAs by Intron Identity. Mol Cell. 2017;67:228-238.e5 pubmed publisher
    ..These results reveal innate immune sensing of circRNA and highlight introns-the predominant output of mammalian transcription-as arbiters of self-nonself identity. ..
  23. Ferdous F, Saski C, Bridges W, Burns M, Dunn H, Elliott K, et al. Bacterial and Viral Products Affect Differential Pattern Recognition Receptor Activation of Chicken Thrombocytes Evidenced through RNA Sequencing. J Immunol. 2017;199:774-781 pubmed publisher
    ..The information reported in this study is useful for defining a limited set of proinflammatory molecules to evaluate in cases of either bacterial or viral disease monitoring. ..