Cellular RNA interacts with MAVS to promote antiviral signaling

Antiviral signaling downstream of RIG-I-like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides or scaffolds. We hypothesized that RNA plays a role in organizing MAVS signaling platforms. We found that MAVS, through its central intrinsically disordered domain, directly interacted with the 3' untranslated regions of cellular messenger RNAs. Elimination of RNA by ribonuclease treatment disrupted the MAVS signalosome, including RNA-modulated MAVS interactors that regulate RLR signaling and viral restriction, and inhibited phosphorylation of transcription factors that induce interferons. This work uncovered a function for cellular RNA in promoting signaling through MAVS and highlights generalizable principles of RNA regulatory control of immune signaling complexes.

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Publication Details

Journal
Science
Published
2024-12-19
DOI
https://doi.org/10.1126/science.adl0429
Citations
32
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
7.70

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article

Cellular RNA interacts with MAVS to promote antiviral signaling

Shao‐En Ong, Michael Gale, Lan H. Chu, Ram Savan et al.
32 citations
Science
interferon and immune responses
7.70
article

Cellular RNA interacts with MAVS to promote antiviral signaling

Shao‐En Ong, Michael Gale, Lan H. Chu, Ram Savan, Nandan S. Gokhale, Andrew Oberst, Emmanuelle Genoyer, Steve Dvorkin, Stacy M. Horner, Kim Somfleth, Moonhee Park, Matthew G. Thompson, Julie Eggenberger, Russell K. Sam, Daphnée M. Marciniak, Julian R. Smith
article en
32 citations

Abstract

Antiviral signaling downstream of RIG-I-like receptors (RLRs) proceeds through a multi-protein complex organized around the adaptor protein mitochondrial antiviral signaling protein (MAVS). Protein complex function can be modulated by RNA molecules that provide allosteric regulation or act as molecular guides or scaffolds. We hypothesized that RNA plays a role in organizing MAVS signaling platforms. We found that MAVS, through its central intrinsically disordered domain, directly interacted with the 3' untranslated regions of cellular messenger RNAs. Elimination of RNA by ribonuclease treatment disrupted the MAVS signalosome, including RNA-modulated MAVS interactors that regulate RLR signaling and viral restriction, and inhibited phosphorylation of transcription factors that induce interferons. This work uncovered a function for cellular RNA in promoting signaling through MAVS and highlights generalizable principles of RNA regulatory control of immune signaling complexes.

ScienceVol. 386(6728)
Duke University (US), University of Washington (US), Alpine Immune Sciences (United States) (US)
National Institutes of Health
Good health and well-being
Openalex Percentile: Top 2%
interferon and immune responses
7.70
DOIOpen Access PDFOpenAlex
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