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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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Drappier, M., Michiels, T. (2018). Ribonuclease L (RNase L). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101861
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