Abstract
Abstract Intracellular detection of RNA or DNA triggers distinct sensors that protect against virus infection: RNA activates the RIG-I-like Receptor (RLR)-MAVS pathway, whereas DNA activates the cyclic GMP-AMP Synthase (cGAS)-STING pathway. In addition, the oligoadenylate synthetases (OAS) detect foreign RNA and form 2'-5'-linked oligoadenylates (2-5A). The sole known function of 2-5A is to activate the endoribonuclease RNase L, which is thought to cleave cellular and viral RNAs indiscriminately into small fragments that activate the RLR response. We show here that, contrary to this prevailing view, RNase L-deficient cells have an enhanced antiviral response to RLR ligands. We find that the in vivo specificity of RNase L is restricted to ribosomal RNA and we establish RNase L as a specific regulator of protein translation, not an indiscriminate mediator of RNA decay. Our findings offer a revised view of the RNase L system, ascribing to it a negative regulatory role in the antiviral response and identifying rRNA as the primary target of RNase L activity. Citation Format: Jonathan Clingan, Sterling Eckard, Daphne Cooper, Hilario Ramos, Jaime Guillen, Bruno Canard, Michael Gale, Jr., Jay Hesselberth, David Barton, Daniel Stetson. Regulation of antiviral immune responses by RNase L [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B133.
Published Version
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