New advances in our understanding of the "unique" RNase L in host pathogen interaction and immune signaling.
Ever since the discovery of the existence of an interferon (IFN)-regulated ribonuclease, significant advances have been made in understanding the mechanism and associated regulatory effects of its action. What had been studied initially as a "unique" endoribonuclease is currently known as ribonuclease L (RNase L where "L" stands for latent). Some of the key developments include discovery of the RNase L signaling pathway, its structural characterization, and its molecular cloning. RNase L has been implicated in antiviral and antibacterial defense, as well as in hereditary prostate cancer. RNase L is activated by 2'-5' linked oligoadenylates (2-5A), which are synthesized by the oligoadenylate synthetases (OASs), a family of IFN-regulated pathogen recognition receptors that sense double-stranded RNAs. Activated RNase L cleaves single stranded RNAs, including viral RNAs and cellular RNAs. The catalytic activity of RNase L has been found to lead into the activation of several cellular signaling pathways, including those involved in autophagy, apoptosis, IFN-β production, NLRP3 inflammasome activation leading to IL-1β secretion, inhibition of cell migration, and cell adhesion. In this review, we will highlight the newest advances in our understanding of the catalytic role of RNase L in the context of different cellular pathways and extend the scope of these findings to discussion of potential therapeutic targets for antimicrobial drug development.
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue Cleveland, OH 44195, USA.
Elona
E
Gusho
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue Cleveland, OH 44195, USA; Pediatrics Division Office, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA(1).
Danika
D
Baskar
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue Cleveland, OH 44195, USA. Electronic address: banerjs2@ccf.org.
Shuvojit
S
Banerjee
D000818:Animals; D004722:Endoribonucleases / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007372:Interferons / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D007372:Interferons; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
2′-5′ Phosphodiesterase; Autophagy; Cell migration; Inflammasome; Influenza A virus; Innate immunity; Oligoadenylate synthetase; Ribonuclease L