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. 2024 Dec 20;386(6728):eadl0429.
doi: 10.1126/science.adl0429. Epub 2024 Dec 20.

Cellular RNA interacts with MAVS to promote antiviral signaling

Nandan S Gokhale  1 , Russell K Sam  1 , Kim Somfleth  1 , Matthew G Thompson  2 , Daphnée M Marciniak  3 , Julian R Smith  1 , Emmanuelle Genoyer  1 , Julie Eggenberger  1 , Lan H Chu  1 , Moonhee Park  2 , Steve Dvorkin  1 , Andrew Oberst  1 , Stacy M Horner  2   4 , Shao-En Ong  3 , Michael Gale Jr  1   5 , Ram Savan  1
Affiliations

Cellular RNA interacts with MAVS to promote antiviral signaling

Nandan S Gokhale et al. Science. .

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.

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Conflict of interest statement

Competing interests:

M.G. is a founder and shareholder in Kineta Inc., and of HDT Bio. The other authors declare that they have no competing interests.

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