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Nat Immunol. 2015 May;16(5):485-94. doi: 10.1038/ni.3132. Epub 2015 Mar 30.

Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.

Author information

1
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.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3
Laboratory of Methyltransferases in Development and Disease, Institute of Molecular and Cell Biology, Singapore.
4
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
5
Microbiome and Disease Tolerance Centre, Department of Microbiology and Immunology, McGill University, Montreal, Canada.
6
The Salk Institute for Biological Studies, La Jolla, California, USA.
7
F. Hoffmann-La Roche, Basel, Switzerland.
8
The University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
9
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.
10
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.

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.

PMID:
25822250
PMCID:
PMC4406851
DOI:
10.1038/ni.3132
[Indexed for MEDLINE]
Free PMC Article

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