title: RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner.
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.
authors.affiliation: 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.
authors.forename: Alys
authors.initials: A
authors.lastname: Peisley
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Sun
authors.initials: S
authors.lastname: Hur
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D009154:Mutation; D025821:Polyubiquitin / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505371:MAVS protein, human; D012330:RNA, Double-Stranded; D011971:Receptors, Immunologic; D025821:Polyubiquitin; D000255:Adenosine Triphosphate; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases