Title: Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. | Journal: Nature structural & molecular biology. 2014 Aug;21(8):671-8 | Authors: Schlundt A, Heinz GA, Janowski R, Geerlof A, Stehle R, Heissmeyer V, Niessing D, Sattler M. | Abstract: 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. | See full PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/25026077 |
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