Open AccessSpliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response
Author(s) -
Nicolas Tremblay,
Martin Baril,
Laurent ChatelChaix,
Salwa Es-Saad,
Alex Young Park,
Robert K. Koenekoop,
Daniel Lamarre
Publication year - 2016
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1005772
Subject(s) - rna helicase a , rig i , small nuclear rna , rna , gene knockdown , biology , spliceosome , rna dependent rna polymerase , virology , rna silencing , sendai virus , microbiology and biotechnology , irf3 , helicase , rna splicing , rna interference , virus , gene , genetics , transcription factor
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.