title: Extensive cooperation of immune master regulators IRF3 and NFκB in RNA Pol II recruitment and pause release in human innate antiviral transcription.
abstract: Transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κB (NFκB) are activated by external stimuli, including virus infection, to translocate to the nucleus and bind genomic targets important for immunity and inflammation. To investigate RNA polymerase II (Pol II) recruitment and elongation in the human antiviral gene regulatory network, a comprehensive genome-wide analysis was conducted during the initial phase of virus infection. Results reveal extensive integration of IRF3 and NFκB with Pol II and associated machinery and implicate partners for antiviral transcription. Analysis indicates that both de novo polymerase recruitment and stimulated release of paused polymerase work together to control virus-induced gene activation. In addition to known messenger-RNA-encoding loci, IRF3 and NFκB stimulate transcription at regions not previously associated with antiviral transcription, including abundant unannotated loci that encode novel virus-inducible RNAs (nviRNAs). These nviRNAs are widely induced by virus infections in diverse cell types and represent a previously overlooked cellular response to virus infection.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Freaney
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kim
authors.forename: Roli
authors.initials: R
authors.lastname: Mandhana
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
mesh_terms: D015870:Gene Expression; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010253:Respirovirus Infections / Q000235:genetics* / Q000276:immunology*; D029082:Sendai virus / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016328:NF-kappa B; D051996:Transcription Factor RelA; D012319:RNA Polymerase II