STING nuclear partners contribute to innate immune signaling responses

Dixon, Charles R.; Malik, Poonam; de las Heras, Jose I.; Saiz-Ros, Natalia; de Lima Alves, Flavia; Tingey, Mark; Gaunt, Eleanor; Richardson, A. Christine; Kelly, David A.; Goldberg, Martin W.; Towers, Greg J.; Yang, Weidong; Rappsilber, Juri; Digard, Paul; Schirmer, Eric C.

doi:10.1016/j.isci.2021.103055

STING nuclear partners contribute to innate immune signaling responses

Dixon, Charles R.; Malik, Poonam; de las Heras, Jose I.; Saiz-Ros, Natalia; de Lima Alves, Flavia; Tingey, Mark; Gaunt, Eleanor; Richardson, A. Christine; Kelly, David A.; Goldberg, Martin W.; Towers, Greg J.; Yang, Weidong; Rappsilber, Juri; Digard, Paul; Schirmer, Eric C.

Authors

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

Professor Martin Goldberg m.w.goldberg@durham.ac.uk
Professor

Greg J. Towers

Weidong Yang

Juri Rappsilber

Paul Digard

Eric C. Schirmer

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.

Citation

Dixon, C. R., Malik, P., de las Heras, J. I., Saiz-Ros, N., de Lima Alves, F., Tingey, M., …Schirmer, E. C. (2021). STING nuclear partners contribute to innate immune signaling responses. iScience, 24(9), https://doi.org/10.1016/j.isci.2021.103055

Journal Article Type	Article
Acceptance Date	Aug 25, 2021
Online Publication Date	Aug 28, 2021
Publication Date	2021
Deposit Date	Nov 15, 2021
Publicly Available Date	Nov 15, 2021
Journal	iScience
Publisher	Cell Press
Peer Reviewed	Peer Reviewed
Volume	24
Issue	9
DOI	https://doi.org/10.1016/j.isci.2021.103055