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' 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.
authors.affiliation: 1] Biomolecular NMR Spectroscopy, Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2] Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Garching, Germany. [3].
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlundt
authors.affiliation: 1] Institute of Molecular Immunology, Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Germany. [2] Institute for Immunology, Ludwig-Maximilians-Universität München, Munich, Germany. [3].
authors.forename: Gitta A
authors.initials: GA
authors.lastname: Heinz
authors.affiliation: 1] Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2].
authors.forename: Robert
authors.initials: R
authors.lastname: Janowski
authors.affiliation: Biomolecular NMR Spectroscopy, Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Arie
authors.initials: A
authors.lastname: Geerlof
authors.affiliation: Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Stehle
authors.affiliation: 1] Institute of Molecular Immunology, Research Unit Molecular Immune Regulation, Helmholtz Zentrum München, Germany. [2] Institute for Immunology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Vigo
authors.initials: V
authors.lastname: Heissmeyer
authors.affiliation: Group Intracellular Transport and RNA Biology, Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Dierk
authors.initials: D
authors.lastname: Niessing
authors.affiliation: 1] Biomolecular NMR Spectroscopy, Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany. [2] Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C501406:Rc3h1 protein, mouse; D044767:Ubiquitin-Protein Ligases