دورية أكاديمية
Macrophage development and activation involve coordinated intron retention in key inflammatory regulators.
العنوان: | Macrophage development and activation involve coordinated intron retention in key inflammatory regulators. |
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المؤلفون: | Green ID; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia., Pinello N; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia., Song R; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia., Lee Q; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.; Immune Imaging Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia., Halstead JM; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia., Kwok CT; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia., Wong ACH; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia., Nair SS; Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst 2010, Australia.; St. Vincent's Clinical School, UNSW, Sydney 2010, Australia.; Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst 2010, Australia., Clark SJ; Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst 2010, Australia.; St. Vincent's Clinical School, UNSW, Sydney 2010, Australia., Roediger B; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.; Immune Imaging Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia., Schmitz U; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Computational Biomedicine Laboratory Centenary Institute, The University of Sydney, Camperdown 2050, Australia., Larance M; Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Camperdown 2006, New South Wales, Australia., Hayashi R; The John Curtin School of Medical Research, The Australian National University, ACT 2601, Australia., Rasko JEJ; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.; Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown 2050, Australia., Wong JJ; Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.; Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia. |
المصدر: | Nucleic acids research [Nucleic Acids Res] 2020 Jul 09; Vol. 48 (12), pp. 6513-6529. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1992- : Oxford : Oxford University Press Original Publication: London, Information Retrieval ltd. |
مواضيع طبية MeSH: | Macrophage Activation* , RNA Splicing*, Macrophages/*immunology , RNA, Messenger/*genetics, Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Cells, Cultured ; Chemokine CXCL2/genetics ; Chemokine CXCL2/metabolism ; Endoglin/genetics ; Endoglin/metabolism ; Humans ; Inhibitor of Differentiation Protein 2/genetics ; Inhibitor of Differentiation Protein 2/metabolism ; Interferon Regulatory Factor-7/genetics ; Interferon Regulatory Factor-7/metabolism ; Introns ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; RNA, Messenger/metabolism ; THP-1 Cells |
مستخلص: | Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/proteins involved in macrophage development and function. We demonstrate that decreased IR in nuclear-detained mRNA is coupled with increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts are rapidly spliced, enabling timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular factors controlling vital regulators of the innate immune response. (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.) |
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المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (CXCL2 protein, human) 0 (Chemokine CXCL2) 0 (ENG protein, human) 0 (Endoglin) 0 (ID2 protein, human) 0 (IRF7 protein, human) 0 (Inhibitor of Differentiation Protein 2) 0 (Interferon Regulatory Factor-7) 0 (LAT protein, human) 0 (Membrane Proteins) 0 (NFKBIZ protein, human) 0 (RNA, Messenger) |
تواريخ الأحداث: | Date Created: 20200526 Date Completed: 20200914 Latest Revision: 20200914 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7337907 |
DOI: | 10.1093/nar/gkaa435 |
PMID: | 32449925 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1362-4962 |
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DOI: | 10.1093/nar/gkaa435 |