TY - JOUR
T1 - Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis
AU - Miller, Matthew S.
AU - Rialdi, Alexander
AU - Ho, Jessica Sook Yuin
AU - Tilove, Micah
AU - Martinez-Gil, Luis
AU - Moshkina, Natasha P.
AU - Peralta, Zuleyma
AU - Noel, Justine
AU - Melegari, Camilla
AU - Maestre, Ana M.
AU - Mitsopoulos, Panagiotis
AU - Madrenas, Joaquín
AU - Heinz, Sven
AU - Benner, Chris
AU - Young, John A.T.
AU - Feagins, Alicia R.
AU - Basler, Christopher F.
AU - Fernandez-Sesma, Ana
AU - Becherel, Olivier J.
AU - Lavin, Martin F.
AU - Van Bakel, Harm
AU - Marazzi, Ivan
N1 - Funding Information:
We thank J. Lim (Icahn School of Medicine at Mount Sinai) for Kunjin virus; M. Evans (Icahn School of Medicine at Mount Sinai) for Gag-Pol; P. Palese (Icahn School of Medicine at Mount Sinai) for comments, anti-PB2 and unpublished observations; A. Telenti for comments; A. García-Sastre (Icahn School of Medicine at Mount Sinai) for comments, RIG-I deficient A549 cells and unpublished observations; R. Roeder (Rockefeller University) for TAF4 reagents; M.F. Lavin (The University of Queensland) for anti-SETX; and the Genomic facility at Icahn and the Proteomics facilities at Rockefeller University. Supported by the computational resources and staff of the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai; the Canadian Institutes of Health Research (M.S.M.); the US National Institutes of Health (U19AI106754 to I.M.); and the National Institute of Allergy and Infectious Diseases Center of Excellence for Influenza Research and Surveillance (HHSN272201400008C to I.M. and H.v.B.).
PY - 2015/5/28
Y1 - 2015/5/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84928582917&partnerID=8YFLogxK
U2 - 10.1038/ni.3132
DO - 10.1038/ni.3132
M3 - Article
C2 - 25822250
AN - SCOPUS:84928582917
SN - 1529-2908
VL - 16
SP - 485
EP - 494
JO - Nature Immunology
JF - Nature Immunology
IS - 5
ER -