STING nuclear partners contribute to innate immune signaling responses

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 9, Pp 103055- (2021)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.103055
Popis: Summary: 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.
Databáze: Directory of Open Access Journals