CELLULAR RNA INTERACTS WITH MAVS TO PROMOTE ANTIVIRAL SIGNALING.

Autor:	Gokhale NS; Department of Immunology, University of Washington, Seattle, WA., Somfleth K; Department of Immunology, University of Washington, Seattle, WA., Thompson MG; Department of Integrative Immunobiology, Duke University, Durham, NC., Sam RK; Department of Immunology, University of Washington, Seattle, WA., Marciniak DM; Department of Pharmacology, University of Washington, Seattle, WA., Chu LH; Department of Immunology, University of Washington, Seattle, WA., Park M; Department of Integrative Immunobiology, Duke University, Durham, NC., Dvorkin S; Department of Immunology, University of Washington, Seattle, WA., Oberst A; Department of Immunology, University of Washington, Seattle, WA., Horner SM; Department of Integrative Immunobiology, Duke University, Durham, NC.; Department of Medicine, Duke University, Durham NC., Ong SE; Department of Pharmacology, University of Washington, Seattle, WA., Gale M Jr; Department of Immunology, University of Washington, Seattle, WA., Savan R; Department of Immunology, University of Washington, Seattle, WA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 25. Date of Electronic Publication: 2023 Sep 25.
DOI:	10.1101/2023.09.25.559083
Abstrakt:	Immune signaling needs to be well-regulated to promote clearance of pathogens, while preventing aberrant inflammation. Interferons (IFNs) and antiviral genes are activated by the detection of viral RNA by RIG-I-like receptors (RLRs). Signal transduction downstream of RLRs proceeds through a multi-protein complex organized around the central adaptor protein MAVS. Recent work has shown that protein complex function can be modulated by RNA molecules providing allosteric regulation or acting as molecular guides or scaffolds. Thus, we hypothesized that RNA plays a role in organizing MAVS signaling platforms. Here, we show that MAVS, through its central intrinsically disordered domain, directly interacts with the 3' untranslated regions of cellular mRNAs. Importantly, elimination of RNA by RNase treatment disrupts the MAVS signalosome, including newly identified regulators of RLR signaling, and inhibits phosphorylation of the transcription factor IRF3. This supports the hypothesis that RNA molecules scaffold proteins in the MAVS signalosome to induce IFNs. Together, this work uncovers a function for cellular RNA in promoting signaling through MAVS and highlights a generalizable principle of RNA regulatory control of cytoplasmic immune signaling complexes. Competing Interests: COMPETING INTERESTS M.G. is a founder and shareholder in Kineta, Inc., and of HDT Bio.
Databáze:	MEDLINE
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