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Mol Cell. 2013 Sep 12;51(5):573-83. doi: 10.1016/j.molcel.2013.07.024. Epub 2013 Aug 29.

RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner.

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1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA.

Abstract

Retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are paralogous receptors for viral double-stranded RNA (dsRNA) with divergent specificity. We have previously shown that MDA5 forms filaments upon viral dsRNA recognition and that this filament formation is essential for interferon signal activation. Here, we show that while RIG-I binds to a dsRNA end as a monomer in the absence of ATP, it assembles in the presence of ATP into a filament that propagates from the dsRNA end to the interior. Furthermore, RIG-I filaments directly stimulate mitochondrial antiviral signaling (MAVS) filament formation without any cofactor, such as polyubiquitin chains, and forced juxtaposition of the isolated signaling domain of RIG-I, as it would be in the filament, is sufficient to activate interferon signaling. Our findings thus define filamentous architecture as a common yet versatile molecular platform for divergent viral RNA detection and proximity-induced signal activation by RIG-I and MDA5.

PMID:
23993742
DOI:
10.1016/j.molcel.2013.07.024
[Indexed for MEDLINE]
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