title: Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response.
abstract: Spliceosomal SNRNP200 is a Ski2-like RNA helicase that is associated with retinitis pigmentosa 33 (RP33). Here we found that SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its amino-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1. We show that SNRNP200 relocalizes into TBK1-containing cytoplasmic structures upon infection, in contrast to the RP33-associated S1087L mutant, which is also unable to rescue antiviral response of SNRNP200 knockdown cells. This functional rescue correlates with the Sec63-1-mediated binding of viral RNA. The hindered IFN-β production of knockdown cells was further confirmed in peripheral blood cells of RP33 patients bearing missense mutation in SNRNP200 upon infection with Sendai virus (SeV). This work identifies a novel immunoregulatory role of the spliceosomal SNRNP200 helicase as an RNA sensor and TBK1 adaptor for the activation of IRF3-mediated antiviral innate response.
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.|Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tremblay
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Baril
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chatel-Chaix
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.
authors.forename: Salwa
authors.initials: S
authors.lastname: Es-Saad
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.|Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Alex Young
authors.initials: AY
authors.lastname: Park
authors.affiliation: Departments of Pediatric Surgery, Human Genetics and Ophthalmology, McGill University, Montréal, Canada.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.affiliation: Centre de Recherche du CHUM (CRCHUM), Montréal, Québec, Canada.|Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamarre
mesh_terms: D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D047468:Immunoprecipitation; D050838:Interferon Regulatory Factor-3 / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D017381:Spliceosomes / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012367:RNA, Viral; D017411:Ribonucleoproteins, Small Nuclear; C545711:SNRNP200 protein, human; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human