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Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation.
Nat. Struct. Mol. Biol. 21, 671-678 (2014)
Roquin function in T cells is essential for the prevention of autoimmune disease. Roquin interacts with the 3′ untranslated regions (UTRs) of co-stimulatory receptors and controls T-cell activation and differentiation. Here we show that the N-terminal ROQ domain from mouse roquin adopts an extended winged-helix (WH) fold, which is sufficient for binding to the constitutive decay element (CDE) in the Tnf 3′ UTR. The crystal structure of the ROQ domain in complex with a prototypical CDE RNA stem-loop reveals tight recognition of the RNA stem and its triloop. Surprisingly, roquin uses mainly non-sequence-specific contacts to the RNA, thus suggesting a relaxed CDE consensus and implicating a broader spectrum of target mRNAs than previously anticipated. Consistently with this, NMR and binding experiments with CDE-like stem-loops together with cell-based assays confirm roquin-dependent regulation of relaxed CDE consensus motifs in natural 3′ UTRs.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Costimulator Messenger-rna; Helper T-cells; Crystal-structure; Autoimmunity; Decay; Degradation; Repression; Family; Domain
Language
english
Publication Year
2014
HGF-reported in Year
2014
ISSN (print) / ISBN
1545-9993
e-ISSN
1545-9985
Quellenangaben
Volume: 21,
Issue: 8,
Pages: 671-678
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Structural Biology (STB)
Institute of Molecular Immunology (IMI)
Research Unit Molecular Immune Regulation (AMIR)
Institute of Molecular Immunology (IMI)
Research Unit Molecular Immune Regulation (AMIR)
POF-Topic(s)
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
Immune Response and Infection
Immune Response and Infection
PSP Element(s)
G-503000-001
G-503091-001
G-501792-001
G-503000-003
G-503091-001
G-501792-001
G-503000-003
PubMed ID
25026077
WOS ID
WOS:000340074300007
Scopus ID
84905656367
Scopus ID
84904271377
Erfassungsdatum
2014-07-14