title: RAVER1 is a coactivator of MDA5-mediated cellular antiviral response.
abstract: Detection of viral nucleic acids by pattern recognition receptors initiates type I interferon (IFN) induction and innate antiviral response. The RIG-I-like receptors (RLRs), including RIG-I and MDA5, recognize cytoplasmic viral RNA in most cell types and are critically involved in innate antiviral response. RIG-I and MDA5 are structurally related and mediate similar signaling pathways. While the regulation of RIG-I activity has been extensively investigated, little is known about the regulatory mechanisms of MDA5 activity. Here we identified ribonucleoprotein PTB-binding 1 (RAVER1) as a specific MDA5-interacting protein. RAVER1 was associated with MDA5 upon viral infection. Overexpression of RAVER1 at low dosages enhanced MDA5- but not RIG-I-mediated activation of the IFN-β promoter, whereas knockdown of RAVER1 inhibited MDA5- but not RIG-I-mediated induction of downstream antiviral genes. Mechanistically, overexpression of RAVER1 enhanced the binding of MDA5 to its ligand poly(I:C), whereas knockdown of RAVER1 had opposite effect. Our findings suggest that RAVER1 specifically regulates MDA5 activity, revealing a mechanism of differential regulation of MDA5- and RIG-I-mediated innate antiviral response.
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: He
authors: H
authors: Chen
authors: Ying
authors: Y
authors: Li
authors: Jing
authors: J
authors: Zhang
authors: Yong
authors: Y
authors: Ran
authors: Jin
authors: J
authors: Wei
authors: Yan
authors: Y
authors: Yang
authors: Hong-Bing
authors: HB
authors: Shu
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007369:Interferon Inducers / Q000494:pharmacology; D000072640:Interferon-Induced Helicase, IFIH1; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic; D012261:Ribonucleoproteins
chemical_list: D002352:Carrier Proteins; D007369:Interferon Inducers; D009687:Nuclear Proteins; C486705:RAVER1 protein, human; D012367:RNA, Viral; D011971:Receptors, Immunologic; D012261:Ribonucleoproteins; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C