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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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
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