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Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.

  • Author(s): Miller, Matthew S
  • Rialdi, Alexander
  • Ho, Jessica Sook Yuin
  • Tilove, Micah
  • Martinez-Gil, Luis
  • Moshkina, Natasha P
  • Peralta, Zuleyma
  • Noel, Justine
  • Melegari, Camilla
  • Maestre, Ana M
  • Mitsopoulos, Panagiotis
  • Madrenas, Joaquín
  • Heinz, Sven
  • Benner, Chris
  • Young, John AT
  • Feagins, Alicia R
  • Basler, Christopher F
  • Fernandez-Sesma, Ana
  • Becherel, Olivier J
  • Lavin, Martin F
  • van Bakel, Harm
  • Marazzi, Ivan
  • et al.

Published Web Location

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.

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