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.

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., Gaunt, E., Richardson, A. C., Kelly, D. A., Goldberg, M. W., Towers, G. J., Yang, W., Rappsilber, J., Digard, P., & 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
• Public URL: https://durham-repository.worktribe.com/output/1222021