STING nuclear partners contribute to innate immune signaling responses
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 t...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221010233 |
| _version_ | 1818358811872722944 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Charles R. Dixon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T20:34:56Z |
| format | Article |
| id | doaj.art-7c77bb3feb48478187feaae2f2cec97e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-13T20:34:56Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-7c77bb3feb48478187feaae2f2cec97e2022-12-21T23:32:18ZengElsevieriScience2589-00422021-09-01249103055STING nuclear partners contribute to innate immune signaling responsesCharles R. Dixon0Poonam Malik1Jose I. de las Heras2Natalia Saiz-Ros3Flavia de Lima Alves4Mark Tingey5Eleanor Gaunt6A. Christine Richardson7David A. Kelly8Martin W. Goldberg9Greg J. Towers10Weidong Yang11Juri Rappsilber12Paul Digard13Eric C. Schirmer14Institute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKDepartment of Biology, Temple University, Philadelphia 19121, USADivision of Infection and Immunity, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UKSchool of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UKSchool of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UKDepartment of Infection and Immunity, University College London, London WC1E 6BT, UKDepartment of Biology, Temple University, Philadelphia 19121, USAInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK; Department of Bioanalytics, Institute of Biotechnology, Technische Universitat Berlin, 13355 Berlin, GermanyDivision of Infection and Immunity, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UKInstitute of Cell Biology, University of Edinburgh, Kings Buildings, Swann 5.22, Mayfield Road, Edinburgh EH9 3BF, UK; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221010233Molecular physiologyImmunologyVirologyCell biology |
| spellingShingle | 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 STING nuclear partners contribute to innate immune signaling responses iScience Molecular physiology Immunology Virology Cell biology |
| title | STING nuclear partners contribute to innate immune signaling responses |
| title_full | STING nuclear partners contribute to innate immune signaling responses |
| title_fullStr | STING nuclear partners contribute to innate immune signaling responses |
| title_full_unstemmed | STING nuclear partners contribute to innate immune signaling responses |
| title_short | STING nuclear partners contribute to innate immune signaling responses |
| title_sort | sting nuclear partners contribute to innate immune signaling responses |
| topic | Molecular physiology Immunology Virology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221010233 |
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