Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response

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. © 2016 tremblay et al.