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Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression.
Nat. Immunol. 11, 725-733 (2010)
The molecular mechanism by which roquin controls the expression of inducible costimulator (ICOS) to prevent autoimmunity remains unsolved. Here we show that in helper T cells, roquin localized to processing (P) bodies and downregulated ICOS expression. The repression was dependent on the RNA helicase Rck, and roquin interacted with Rck and the enhancer of decapping Edc4, which act together in mRNA decapping. Sequences in roquin that confer P-body localization were essential for roquin-mediated ICOS repression. However, this process did not require microRNAs or the RNA-induced silencing complex (RISC). Instead, roquin bound ICOS mRNA directly, showing an intrinsic preference for a previously unrecognized sequence in the 3' untranslated region (3' UTR). Our results support a model in which roquin controls ICOS expression through binding to the 3' UTR of ICOS mRNA and by interacting with proteins that confer post-transcriptional repression.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
3' Untranslated Regions; Amino Acid Sequence; Animals; Antigens; Differentiation; T-Lymphocyte/genetics; Antigens; Differentiation; T-Lymphocyte/immunology*; Autoimmunity/genetics; Autoimmunity/immunology; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; DEAD-box RNA Helicases/genetics; DEAD-box RNA Helicases/immunology*; Gene Expression Regulation; Mice; Mice; Mutant Strains; Mice; Transgenic; MicroRNAs/genetics*; MicroRNAs/immunology; Proto-Oncogene Proteins/genetics; Proto-On
Language
english
Publication Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
1529-2908
e-ISSN
1529-2916
Journal
Nature Immunology
Quellenangaben
Volume: 11,
Issue: 8,
Pages: 725-733
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes and Regeneration Research (IDR)
Research Unit Molecular Immune Regulation (AMIR)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes and Regeneration Research (IDR)
Research Unit Molecular Immune Regulation (AMIR)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30502 - Diabetes: Pathophysiology, Prevention and Therapy
90000 - German Center for Diabetes Research
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30502 - Diabetes: Pathophysiology, Prevention and Therapy
90000 - German Center for Diabetes Research
Research field(s)
Immune Response and Infection
Helmholtz Diabetes Center
Immune Response and Infection
Helmholtz Diabetes Center
PSP Element(s)
G-551000-001
G-501700-003
G-501792-001
G-553100-001
G-501793-001
G-501900-232
G-501700-003
G-501792-001
G-553100-001
G-501793-001
G-501900-232
PubMed ID
20639877
DOI
10.1038/ni.1902
WOS ID
000280149400014
Scopus ID
77954959530
Erfassungsdatum
2010-07-18