Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis.

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Miller MS,Rialdi A,Ho JS,Tilove M,Martinez-Gil L,Moshkina NP,Peralta Z,Noel J,Melegari C,Maestre AM,Mitsopoulos P,Madrenas J,Heinz S,Benner C,Young JA,Feagins AR,Basler CF,Fernandez-Sesma A,Becherel OJ,Lavin MF,va

doi

10.1038/ni.3132

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

485-94

issue

5

eissn

1529-2908

issn

1529-2916

pii

ni.3132

journal_volume

16

pub_type

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