Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription

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) recruitmen...

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Main Authors: Jonathan E. Freaney, Rebecca Kim, Roli Mandhana, Curt M. Horvath
Format: Article
Language:English
Published: Elsevier 2013-09-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124713004051
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spelling doaj-3fa0af81051c4ae2b4fbdd4ba11a9a9a2020-11-25T01:07:40ZengElsevierCell Reports2211-12472013-09-014595997310.1016/j.celrep.2013.07.043Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral TranscriptionJonathan E. Freaney0Rebecca Kim1Roli Mandhana2Curt M. Horvath3Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USADepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA 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. http://www.sciencedirect.com/science/article/pii/S2211124713004051
collection DOAJ
language English
format Article
sources DOAJ
author Jonathan E. Freaney
Rebecca Kim
Roli Mandhana
Curt M. Horvath
spellingShingle Jonathan E. Freaney
Rebecca Kim
Roli Mandhana
Curt M. Horvath
Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
Cell Reports
author_facet Jonathan E. Freaney
Rebecca Kim
Roli Mandhana
Curt M. Horvath
author_sort Jonathan E. Freaney
title Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
title_short Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
title_full Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
title_fullStr Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
title_full_unstemmed Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
title_sort extensive cooperation of immune master regulators irf3 and nfκb in rna pol ii recruitment and pause release in human innate antiviral transcription
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2013-09-01
description 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.
url http://www.sciencedirect.com/science/article/pii/S2211124713004051
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