Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis

Matthew S. Miller, Alexander Rialdi, Jessica Sook Yuin Ho, Micah Tilove, Luis Martinez-Gil, Natasha P. Moshkina, Zuleyma Peralta, Justine Noel, Camilla Melegari, Ana M. Maestre, Panagiotis Mitsopoulos, Joaquín Madrenas, Sven Heinz, Chris Benner, John A.T. Young, Alicia R. Feagins, Christopher F. Basler, Ana Fernandez-Sesma, Olivier J. Becherel, Martin F. LavinHarm Van Bakel, Ivan Marazzi

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish
Pages (from-to)485-494
Number of pages10
JournalNature Immunology
Volume16
Issue number5
DOIs
StatePublished - 28 May 2015

Fingerprint

Dive into the research topics of 'Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis'. Together they form a unique fingerprint.

Cite this