Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Ribonuclease L (RNase L)

  • Melissa Drappier
  • Thomas Michiels
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101861

Synonyms

 PRCA1;  RNS4

Historical Background

In early stages of viral infection, the innate immune response and particularly the interferon response play a critical role in restricting viral replication and propagation, awaiting the establishment of the adaptive immune response. One of the best-described IFN-dependent antiviral responses is the OAS/RNase L pathway. This two-component system is controlled by type I and type III interferons (IFN). Back in the 1970s, the groups of I. Kerr and P. Lengyel discovered a cellular endoribonuclease (RNase) activity that was increased by IFN and depended on the presence of double-stranded RNA (dsRNA) (Brown et al. 1976; Kerr et al. 1977). Further, a correlation was found between this RNase activity and the synthesis of unusual 2′-5′ oligoadenylates (2-5A) (Fig. 1) by a family of enzymes called oligoadenylate synthetases (OAS) [(Baglioni et al. 1978), reviewed by (Hovanessian and Justesen 2007)].
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References

  1. Baglioni C, Minks MA, Maroney PA. Interferon action may be mediated by activation of a nuclease by pppA2′p5′A2′p5′A. Nature. 1978;273:684–7.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bisbal C, Silverman RH. Diverse functions of RNase L and implications in pathology. Biochimie. 2007;89:789–98.  https://doi.org/10.1016/j.biochi.2007.02.006.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Brennan-Laun SE, Li XL, Ezelle HJ, Venkataraman T, Blackshear PJ, Wilson GM, et al. RNase L attenuates mitogen-stimulated gene expression via transcriptional and post-transcriptional mechanisms to limit the proliferative response. J Biol Chem. 2014;289:33629–43.  https://doi.org/10.1074/jbc.M114.589556.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Brown GE, Lebleu B, Kawakita M, Shaila S, Sen GC, Lengyel P. Increased endonuclease activity in an extract from mouse Ehrlich ascites tumor cells which had been treated with a partially purified interferon preparation: dependence of double-stranded RNA. Biochem Biophys Res Commun. 1976;69:114–22.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Burgess HM, Mohr I. Cellular 5′-3′ mRNA exonuclease Xrn1 controls double-stranded RNA accumulation and anti-viral responses. Cell Host Microbe. 2015;17:332–44.  https://doi.org/10.1016/j.chom.2015.02.003.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Chakrabarti A, Ghosh PK, Banerjee S, Gaughan C, Silverman RH. RNase L triggers autophagy in response to viral infections. J Virol. 2012;86:11311–21.  https://doi.org/10.1128/JVI.00270-12.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chakrabarti A, Banerjee S, Franchi L, Loo YM, Gale Jr M, Nunez G, et al. RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe. 2015;17:466–77.  https://doi.org/10.1016/j.chom.2015.02.010.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Dong B, Silverman RH. Alternative function of a protein kinase homology domain in 2′, 5′-oligoadenylate dependent RNase L. Nucleic acids research. 1999;27:439–45.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Drappier M, Michiels T. Inhibition of the OAS/RNase L pathway by viruses. Curr Opin Virol. 2015.  https://doi.org/10.1016/j.coviro.2015.07.002.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Ezelle HJ, Malathi K, Hassel BA. The roles of RNase-L in antimicrobial immunity and the cytoskeleton-associated innate response. Int J Mol Sci. 2016;17.  https://doi.org/10.3390/ijms17010074.
  11. Gusho E, Baskar D, Banerjee S. New advances in our understanding of the “unique” RNase L in host pathogen interaction and immune signaling. Cytokine. 2016.  https://doi.org/10.1016/j.cyto.2016.08.009.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Han Y, Whitney G, Donovan J, Korennykh A. Innate immune messenger 2-5A tethers human RNase L into active high-order complexes. Cell Rep. 2012;2:902–13.  https://doi.org/10.1016/j.celrep.2012.09.004.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Han Y, Donovan J, Rath S, Whitney G, Chitrakar A, Korennykh A. Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response. Science. 2014;343:1244–8.  https://doi.org/10.1126/science.1249845.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hovanessian AG, Justesen J. The human 2′-5′oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2′-5′ instead of 3′-5′ phosphodiester bond formation. Biochimie. 2007;89:779–88.  https://doi.org/10.1016/j.biochi.2007.02.003.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Huang H, Zeqiraj E, Dong B, Jha BK, Duffy NM, Orlicky S, et al. Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon-induced antiviral activity. Mol Cell. 2014;53:221–34.  https://doi.org/10.1016/j.molcel.2013.12.025.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kerr IM, Brown RE, Hovanessian AG. Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA. Nature. 1977;268:540–2.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Lee KP, Dey M, Neculai D, Cao C, Dever TE, Sicheri F. Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell. 2008;132:89–100.  https://doi.org/10.1016/j.cell.2007.10.057.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Le Roy F, Salehzada T, Bisbal C, Dougherty JP, Peltz SW. A newly discovered function for RNase L in regulating translation termination. Nat Struct Mol Biol. 2005;12:505–12.  https://doi.org/10.1038/nsmb944.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Le Roy F, Silhol M, Salehzada T, Bisbal C. Regulation of mitochondrial mRNA stability by RNase L is translation-dependent and controls IFN alpha-induced apoptosis. Cell Death Differ. 2007;14:1406–13.  https://doi.org/10.1038/sj.cdd.4402130.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Liu SW, Katsafanas GC, Liu R, Wyatt LS, Moss B. Poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsRNA and the induction of innate antiviral responses. Cell Host Microbe. 2015;17:320–31.  https://doi.org/10.1016/j.chom.2015.02.002.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Malathi K, Dong B, Gale Jr M, Silverman RH. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature. 2007;448:816–9.  https://doi.org/10.1038/nature06042.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Martinand C, Salehzada T, Silhol M, Lebleu B, Bisbal C. The RNase L inhibitor (RLI) is induced by double-stranded RNA. J Interf Cytokine Res. 1998;18:1031–8.CrossRefGoogle Scholar
  23. Siddiqui MA, Malathi K. RNase L induces autophagy via c-Jun N-terminal kinase and double-stranded RNA-dependent protein kinase signaling pathways. J Biol Chem. 2012;287:43651–64.  https://doi.org/10.1074/jbc.M112.399964.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Sorgeloos F, Jha BK, Silverman RH, Michiels T. Evasion of antiviral innate immunity by Theiler’s virus L* protein through direct inhibition of RNase L. PLoS Pathog. 2013;9:e1003474.  https://doi.org/10.1371/journal.ppat.1003474.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Thornbrough JM, Jha BK, Yount B, Goldstein SA, Li Y, Elliott R, et al. Middle East respiratory syndrome coronavirus NS4b protein inhibits host RNase L activation. MBio. 2016;7:e00258.  https://doi.org/10.1128/mBio.00258-16.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Townsend HL, Jha BK, Han JQ, Maluf NK, Silverman RH, Barton DJ. A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L. RNA. 2008;14:1026–36.  https://doi.org/10.1261/rna.958908.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Zhao L, Jha BK, Wu A, Elliott R, Ziebuhr J, Gorbalenya AE, et al. Antagonism of the interferon-induced OAS-RNase L pathway by murine coronavirus ns2 protein is required for virus replication and liver pathology. Cell Host Microbe. 2012;11:607–16.  https://doi.org/10.1016/j.chom.2012.04.011.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Zhou A, Hassel BA, Silverman RH. Expression cloning of 2-5A-dependent RNAse: a uniquely regulated mediator of interferon action. Cell. 1993;72:753–65.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Zhou A, Paranjape J, Brown TL, Nie H, Naik S, Dong B, et al. Interferon action and apoptosis are defective in mice devoid of 2′,5′-oligoadenylate-dependent RNase L. EMBO J. 1997;16:6355–63.  https://doi.org/10.1093/emboj/16.21.6355.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.de Duve InstituteUniversité catholique de LouvainBrusselsBelgium