Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis
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..
Medienart: |
Artikel |
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Erscheinungsjahr: |
2015 |
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Erschienen: |
2015 |
Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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Enthalten in: |
Nature immunology - 16(2015), 5, Seite 485-494 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Miller, Matthew S [VerfasserIn] |
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Links: |
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doi: |
10.1038/ni.3132 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
OLC1961009773 |
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100 | 1 | |a Miller, Matthew S |e verfasserin |4 aut | |
245 | 1 | 0 | |a Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis |
264 | 1 | |c 2015 | |
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520 | |a 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. | ||
650 | 4 | |a RNA Helicases - metabolism | |
650 | 4 | |a Immunity, Innate - genetics | |
650 | 4 | |a RNA Polymerase II - metabolism | |
650 | 4 | |a RNA, Small Interfering - genetics | |
650 | 4 | |a RNA Helicases - genetics | |
650 | 4 | |a Cytokines - metabolism | |
650 | 4 | |a Influenza, Human - immunology | |
650 | 4 | |a Interferon Regulatory Factor-3 - metabolism | |
650 | 4 | |a Amyotrophic Lateral Sclerosis - genetics | |
650 | 4 | |a Virus Replication - genetics | |
650 | 4 | |a Spinocerebellar Degenerations - genetics | |
650 | 4 | |a RNA Polymerase II - genetics | |
650 | 4 | |a Orthomyxoviridae - physiology | |
650 | 4 | |a West Nile Fever - immunology | |
650 | 4 | |a West Nile virus - physiology | |
700 | 1 | |a Rialdi, Alexander |4 oth | |
700 | 1 | |a Ho, Jessica Sook Yuin |4 oth | |
700 | 1 | |a Tilove, Micah |4 oth | |
700 | 1 | |a Martinez-Gil, Luis |4 oth | |
700 | 1 | |a Moshkina, Natasha P |4 oth | |
700 | 1 | |a Peralta, Zuleyma |4 oth | |
700 | 1 | |a Noel, Justine |4 oth | |
700 | 1 | |a Melegari, Camilla |4 oth | |
700 | 1 | |a Maestre, Ana M |4 oth | |
700 | 1 | |a Mitsopoulos, Panagiotis |4 oth | |
700 | 1 | |a Madrenas, Joaquín |4 oth | |
700 | 1 | |a Heinz, Sven |4 oth | |
700 | 1 | |a Benner, Chris |4 oth | |
700 | 1 | |a Young, John A T |4 oth | |
700 | 1 | |a Feagins, Alicia R |4 oth | |
700 | 1 | |a Basler, Christopher F |4 oth | |
700 | 1 | |a Fernandez-Sesma, Ana |4 oth | |
700 | 1 | |a Becherel, Olivier J |4 oth | |
700 | 1 | |a Lavin, Martin F |4 oth | |
700 | 1 | |a van Bakel, Harm |4 oth | |
700 | 1 | |a Marazzi, Ivan |4 oth | |
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856 | 4 | 1 | |u http://dx.doi.org/10.1038/ni.3132 |3 Volltext |
856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25822250 |
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