Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

RIG-I (Retinoic Acid Inducible Gene-I)

  • Nazish Abdullah
  • Shaikh Muhammad Atif
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101512

Synonyms

Historical Background

RIG-I (retinoic acid-inducible gene-I, DDX58) is the founding member of the family of RIG-I like receptors (RLRs) that have been demonstrated to have a role in antiviral immunity. It was first reported in Pig by Zhang et al. as a helicase induced during reproductive and respiratory syndrome virus replication (Zhang et al. 2000). In 2004, Yoneyama et al. identified RIG-I as a sensor of viral RNA using a cDNA library screen of molecules that potently enhanced type-I IFN production in response to dsRNA molecules (Yoneyama et al. 2004). RIG-I is a cytoplasmic pattern recognition receptor that belongs to the class of ATP-dependent helicases. This class also includes MDA5 and LGP2. RIG-I is described to have three different domains each with different functions. It has a tandem CARD domain at the N-terminus, a central helicase/ATPase domain, and a C-terminal domain (CTD). The C-terminal domain or...

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References

  1. Chan YK, Gack MU. Viral evasion of intracellular DNA and RNA sensing. Nat Rev Microbiol. 2016;14(6):360–73.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Cui S, Eisenächer K, Kirchhofer A, Brzózka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP. The C-terminal regulatory domain is the RNA 5′-triphosphate sensor of RIG-I. Mol Cell. 2008;29(2):169–79.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Duewell P, Steger A, Lohr H, Bourhis H, Hoelz H, Kirchleitner SV, Stieg MR, Grassmann S, Kobold S, Siveke JT, Endres S, Schnurr M. RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8+ T cells. Cell Death Differ. 2014;21(12):1825–37.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature. 2007;446(7138):916–20.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gao D, Yang YK, Wang RP, Zhou X, Diao FC, Li MD, Zhai ZH, Jiang ZF, Chen DY. REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PLoS One. 2009;4(6):e5760.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Gates LT, Shisler JL. cFLIPL interrupts IRF3–CBP–DNA interactions to inhibit IRF3-driven transcription. J Immunol. 2016;197(3):923–33.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Horner SM, Liu HM, Park HS, Briley J, Gale Jr M. Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci USA. 2011;108(35):14590–5.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146(3):448–61.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O, Akira S. Cell type-specific involvement of RIG-I in antiviral response. Immunity. 2005;23(1):19–28.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005;6(10):981–8.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Lei CQ, Zhang Y, Xia T, Jiang LQ, Zhong B, Shu HB. FoxO1 negatively regulates cellular antiviral response by promoting degradation of IRF3. J Biol Chem. 2013;288(18):12596–604.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Li S, Zheng H, Mao AP, Zhong B, Li Y, Liu Y, Gao Y, Ran Y, Tien P, Shu HB. Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6. J Biol Chem. 2010;285(7):4291–7.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Li MT, Di W, Xu H, Yang YK, Chen HW, Zhang FX, Zhai ZH, Chen DY. Negative regulation of RIG-I-mediated innate antiviral signaling by SEC14L1. J Virol. 2013;87(18):10037–46.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Liu X, Cai X, Zhang D, Xu C, Xiao W. Zebrafish foxo3b negatively regulates antiviral response through suppressing the transactivity of irf3 and irf7. J Immunol. 2016;197(12):4736–49.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lu C, Xu H, Ranjith-Kumar CT, Brooks MT, Hou TY, Hu F, Herr AB, Strong RK, Kao CC, Li P. The structural basis of 5′ triphosphate double-stranded RNA recognition by RIG-I C-terminal domain. Structure. 2010;18(8):1032–43.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Maharaj NP, Wies E, Stoll A, Gack MU. Conventional protein kinase C-α (PKC-α) and PKC-β negatively regulate RIG-I antiviral signal transduction. J Virol. 2012;86(3):1358–71.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Mao AP, Li S, Zhong B, Li Y, Yan J, Li Q, Teng C, Shu HB. Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response. J Biol Chem. 2010;285(13):9470–6.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437(7062):1167–72.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Nazmi A, Mukhopadhyay R, Dutta K, Basu A. STING mediates neuronal innate immune response following Japanese encephalitis virus infection. Sci Rep. 2012;2:347.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Patel JR, Jain A, Chou YY, Baum A, Ha T, García-Sastre A. ATPase-driven oligomerization of RIG-I on RNA allows optimal activation of type-I interferon. EMBO Rep. 2013;14(9):780–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Peisley A, Wu B, Yao H, Walz T, Hur S. RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner. Mol Cell. 2013;51(5):573–83.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Rajsbaum R, García-Sastre A, Versteeg GA. TRIMmunity: The roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. Mol Biol. 2014;426(6):1265–84.CrossRefGoogle Scholar
  23. Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale Jr M. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA. 2007;104(2):582–7.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Schlee M, Hartmann G. The chase for the RIG-I ligand—recent advances. Mol Ther. 2010;18(7):1254–62.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122(5):669–82.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Sumpter Jr R, Loo YM, Foy E, Li K, Yoneyama M, Fujita T, Lemon SM, Gale Jr M. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase. RIG-I J Virol. 2005;79(5):2689–99.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Sun Z, Ren H, Liu Y, Teeling JL, Gu J. Phosphorylation of RIG-I by casein kinase II inhibits its antiviral response. J Virol. 2011;85(2):1036–47.  https://doi.org/10.1128/JVI.01734-10.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale Jr M, Inagaki F, Fujita T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell. 2008;29(4):428–40.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010 Mar 19;140(6):805–20.  https://doi.org/10.1016/j.cell.2010.01.022.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19(6):727–40.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, de la Cruz MJ, Borkowski B, Zhang X, Chen ZJ, Jiang QX. Structural basis for the prion-like MAVS filaments in antiviral innate immunity. elife. 2014;3:e01489.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Xu L, Wang W, Li Y, Zhou X, Yin Y, Wang Y, de Man RA, van der Laan LJ, Huang F, Kamar N, Peppelenbosch MP, Pan Q RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus dispensable of interferon production. Hepatology 2017.  https://doi.org/10.1002/hep.29105.
  33. Yang YK, Qu H, Gao D, Di W, Chen HW, Guo X, Zhai ZH, Chen DY. RF-like protein 16 (ARL16) inhibits RIG-I by binding with its C-terminal domain in a GTP-dependent manner. J Biol Chem. 2011;286(12):10568–80.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol. 2004 Jul;5(7):730–7.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Yoneyama M, Onomoto K, Jogi M, Akaboshi T, Fujita T. Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol. 2015;32:48–53.  https://doi.org/10.1016/j.coi.2014.12.012. Epub 2015 Jan 14.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Zhang X, Wang C, Schook LB, Hawken RJ, Rutherford MS. An RNA helicase, RHIV -1, induced by porcine reproductive and respiratory syndrome virus (PRRSV) is mapped on porcine chromosome 10q13. Microb Pathog. 2000;28(5):267–78.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Zhu H, Xu W-Y, Hu Z, Zhang H, Shen Y, Lu S, Wei C, Wang Z-G. RNA virus receptor Rig-I monitors gut microbiota and inhibit colitis-associated colorectal cancer. J Exp Clin Cancer Res. 2017;36:2.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of BiochemistryWeill Cornell MedicineNew YorkUSA
  2. 2.Department of PediatricsNational Jewish HealthDenverUSA