title: RNase L and the NLRP3-inflammasome: An old merchant in a new trade.
abstract: The type I/III interferon (IFN)-inducible 2'-5'- oligoadenylate synthetase (OAS)/endoribonuclease L (RNase L) is a classical innate immune pathway that has been implicated in antiviral and antibacterial defense and also in hereditary prostate cancer. The OAS/RNase L pathway is activated when OAS senses double-stranded RNA and catalyzes the synthesis of 2'-5' linked oligodenylates (2-5A) from ATP. 2-5A then binds and activates RNase L, resulting cleavage of single-stranded RNAs. RNase L cleavage products are capable of activating RIG-like receptors such as RIG-I and MDA5 that leads to IFN-β expression during viral infection. Our recent findings suggest that beside the RLR pathway, RNase L cleavage products can also activate the NLRP3-inflammasome pathway, which requires DHX33 (DExD/H-box helicase) and the mitochondrial adaptor protein MAVS. Here we discuss this newly identified role of OAS-RNase L pathway in regulation of inflammasome signaling as an alternative antimicrobial mechanism that has potential as a target for development of new broad-spectrum antimicrobial and anti-inflammatory therapies.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: banerjs2@ccf.org.
authors.forename: Shuvojit
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D000071457:DEAD Box Protein 58 / Q000276:immunology; D053487:DEAD-box RNA Helicases / Q000276:immunology; D004722:Endoribonucleases / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology*; D000072640:Interferon-Induced Helicase, IFIH1 / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology; D011971:Receptors, Immunologic
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D016899:Interferon-beta; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; C452820:RIGI protein, human; C568925:DHX33 protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1
keywords: 2-5A; IAV; NLRP3; OAS; RNase L