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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)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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
Quellenangaben Volume: 11, Issue: 8, Pages: 725-733 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
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
Research field(s)
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
PubMed ID 20639877
Scopus ID 77954959530
Erfassungsdatum 2010-07-18