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

doi:10.1016/j.isci.2021.103055

STING nuclear partners contribute to innate immune signaling responses

iScience. 2021 Aug 28;24(9):103055. doi: 10.1016/j.isci.2021.103055. eCollection 2021 Sep 24.

Authors

Affiliations

¹ Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK.
² Department of Biology, Temple University, Philadelphia 19121, USA.
³ Division of Infection and Immunity, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK.
⁴ School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK.
⁵ Department of Infection and Immunity, University College London, London WC1E 6BT, UK.
⁶ Department of Bioanalytics, Institute of Biotechnology, Technische Universitat Berlin, 13355 Berlin, Germany.

Abstract

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.

Keywords: Cell biology; Immunology; Molecular physiology; Virology.

Abstract

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