@article{3f57b0a296e0449eb7803a1efbb47717,
title = "Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation",
abstract = "Roquin function in T cells is essential for the prevention of autoimmune disease. Roquin interacts with the 3' €2 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' €2 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' €2 UTRs.",
author = "Andreas Schlundt and Heinz, {Gitta A.} and Robert Janowski and Arie Geerlof and Ralf Stehle and Vigo Heissmeyer and Dierk Niessing and Michael Sattler",
note = "Funding Information: SCHL2062/1-1 (to A.S.), SFB1035 and GRK1721 (to M.S.), NI-1110/4-1 (to D.N.), SFB646 and FOR855 (to D.N.) and SFB1054 TP-A03 (to V.H.) and by the European Commission through a European Research Council grant to V.H. Funding Information: We acknowledge the use of the X-ray crystallography platform and the protein expression and purification facility of the Helmholtz Zentrum M{\"u}nchen, the Bavarian NMR Center, and SAXS measurements at the facility of the SFB1035, Technische Universit{\"a}t M{\"u}nchen. We thank S. Hauck (Helmholtz Zentrum M{\"u}nchen) and J. Winter (Technische Universit{\"a}t M{\"u}nchen) for MS analysis and A. Berns (The Netherlands Cancer Institute) for providing the Cre-ERT2 mouse line. G.A.H. acknowledges the Boehringer Ingelheim Fonds for a PhD fellowship. This work was supported by the Deutsche Forschungsgemeinschaft through grants",
year = "2014",
month = aug,
doi = "10.1038/nsmb.2855",
language = "English",
volume = "21",
pages = "671--678",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Research",
number = "8",
}