Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.
Matthew S MillerAlexander RialdiJessica Sook Yuin HoMicah TiloveLuis Martinez-GilNatasha P MoshkinaZuleyma PeraltaJustine NoelCamilla MelegariAna M MaestrePanagiotis MitsopoulosJoaquín MadrenasSven HeinzChris BennerJohn A T YoungAlicia R FeaginsChristopher F BaslerAna Fernandez-SesmaOlivier J BecherelMartin F LavinHarm van BakelIvan MarazziPublished in: Nature immunology (2015)
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.
Keyphrases
- induced apoptosis
- amyotrophic lateral sclerosis
- cell cycle arrest
- wild type
- endoplasmic reticulum stress
- gene expression
- emergency department
- cell death
- poor prognosis
- oxidative stress
- sars cov
- transcription factor
- machine learning
- patient safety
- early onset
- electronic health record
- cell proliferation
- big data
- deep learning
- antimicrobial resistance
- heat stress
- quality improvement
- artificial intelligence
- heat shock protein
- pluripotent stem cells