STING Nuclear Partners Contribute to Innate Immune Signalling Responses

Charles Dixon, Poonam Malik, Jose de las Heras, Natalia Saiz ros, Flaviade Lima Alves, Mark Tingey, Eleanor Gaunt, A Christine Richardson, David Kelly, Martin Goldberg, Greg J Towers, Weidong Yang, Juri Rappsilber, Paul Digard, Eric C. Schirmer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

STING is an adaptor for cytoplasmic DNA sensing by cGAMP/cGAS that helps trigger innate immune responses (IIR). Although STING is mostly localised 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, AATF as novel modulators of dsDNA triggered IIR. 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.
Original languageEnglish
Article number103055
JournaliScience
Early online date28 Aug 2021
DOIs
Publication statusE-pub ahead of print - 28 Aug 2021

Keywords

  • nuclear envelope
  • NET23
  • STING
  • innate immune response
  • SYNCRIP
  • influenza A virus

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