STING nuclear partners contribute to innate immune signaling responses
Charles R. Dixon,
Poonam Malik,
Jose I. de las Heras,
Natalia Saiz-Ros,
Flavia de Lima Alves,
Mark Tingey,
Eleanor Gaunt,
A. Christine Richardson,
David A. Kelly,
Martin W. Goldberg,
Greg J. Towers,
Weidong Yang,
Juri Rappsilber,
Paul Digard,
Eric C. Schirmer
Affiliations
Charles R. Dixon
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Poonam Malik
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Jose I. de las Heras
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Natalia Saiz-Ros
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Flavia de Lima Alves
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Mark Tingey
Department of Biology, Temple University, Philadelphia 19121, USA
Eleanor Gaunt
Division of Infection and Immunity, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK
A. Christine Richardson
School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK
David A. Kelly
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK
Martin W. Goldberg
School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK
Greg J. Towers
Department of Infection and Immunity, University College London, London WC1E 6BT, UK
Weidong Yang
Department of Biology, Temple University, Philadelphia 19121, USA
Juri Rappsilber
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK; Department of Bioanalytics, Institute of Biotechnology, Technische Universitat Berlin, 13355 Berlin, Germany
Paul Digard
Division of Infection and Immunity, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK
Eric C. Schirmer
Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK; Corresponding author
Summary: STimulator of INterferon Genes (STING) is an adaptor for cytoplasmic DNA sensing by cGAMP/cGAS that helps trigger innate immune responses (IIRs). Although STING is mostly localized in the ER, we find a separate inner nuclear membrane pool of STING that increases mobility and redistributes to the outer nuclear membrane upon IIR stimulation by transfected dsDNA or dsRNA mimic poly(I:C). Immunoprecipitation of STING from isolated nuclear envelopes coupled with mass spectrometry revealed a distinct nuclear envelope-STING proteome consisting of known nuclear membrane proteins and enriched in DNA- and RNA-binding proteins. Seventeen of these nuclear envelope STING partners are known to bind direct interactors of IRF3/7 transcription factors, and testing a subset of these revealed STING partners SYNCRIP, MEN1, DDX5, snRNP70, RPS27a, and AATF as novel modulators of dsDNA-triggered IIRs. Moreover, we find that SYNCRIP is a novel antagonist of the RNA virus, influenza A, potentially shedding light on reports of STING inhibition of RNA viruses.
