Dissemin is shutting down on January 1st, 2025

Published in

Nature Research, Nature Structural and Molecular Biology, 8(21), p. 671-678, 2014

DOI: 10.1038/nsmb.2855

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Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation.

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.