title: Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.
abstract: The human helicase senataxin (SETX) has been linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS4) and ataxia with oculomotor apraxia (AOA2). Here we identified a role for SETX in controlling the antiviral response. Cells that had undergone depletion of SETX and SETX-deficient cells derived from patients with AOA2 had higher expression of antiviral mediators in response to infection than did wild-type cells. Mechanistically, we propose a model whereby SETX attenuates the activity of RNA polymerase II (RNAPII) at genes stimulated after a virus is sensed and thus controls the magnitude of the host response to pathogens and the biogenesis of various RNA viruses (e.g., influenza A virus and West Nile virus). Our data indicate a potentially causal link among inborn errors in SETX, susceptibility to infection and the development of neurologic disorders.
authors.affiliation: 1] Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Biochemistry and Biomedical Sciences, Institute for Infectious Diseases Research, McMaster Immunology Research Centre, McMaster University, Hamilton, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Miller
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rialdi
authors.affiliation: Laboratory of Methyltransferases in Development and Disease, Institute of Molecular and Cell Biology, Singapore.
authors.forename: Jessica Sook Yuin
authors.identifier: 0000000322342602
authors.initials: JS
authors.lastname: Ho
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Micah
authors.initials: M
authors.lastname: Tilove
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Gil
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Natasha P
authors.initials: NP
authors.lastname: Moshkina
authors.affiliation: Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Zuleyma
authors.initials: Z
authors.lastname: Peralta
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Noel
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Camilla
authors.initials: C
authors.lastname: Melegari
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Maestre
authors.affiliation: Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Canada.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mitsopoulos
authors.affiliation: Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Canada.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Madrenas
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, California, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Heinz
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, California, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: John A T
authors.initials: JA
authors.lastname: Young
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Feagins
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Becherel
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
authors.affiliation: 1] Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Harm
authors.identifier: 0000000213766916
authors.initials: H
authors.lastname: van Bakel
authors.affiliation: 1] Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Marazzi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D004265:DNA Helicases; D004285:Dogs; D015536:Down-Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007251:Influenza, Human / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D064251:Multifunctional Enzymes; D009975:Orthomyxoviridae / Q000502:physiology*; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000151:congenital; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000502:physiology*
chemical_list: D016207:Cytokines; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D064251:Multifunctional Enzymes; D034741:RNA, Small Interfering; D012319:RNA Polymerase II; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases
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