Skip to main content

Research Repository

Advanced Search

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.

STING nuclear partners contribute to innate immune signaling responses Thumbnail


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

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

Files






You might also like



Downloadable Citations