title: Roquin binding to target mRNAs involves a winged helix-turn-helix motif.
abstract: Roquin proteins mediate mRNA deadenylation by recognizing a conserved class of stem-loop RNA degradation motifs via their Roquin domain. Here we present the crystal structure of a Roquin domain, revealing a mostly helical protein fold bearing a winged helix-turn-helix motif. By combining structural, biochemical and mutation analyses, we gain insight into the mode of RNA binding. We show that the winged helix-turn-helix motif is involved in the binding of constitutive decay elements-containing stem-loop mRNAs. Moreover, we provide biochemical evidence that Roquin proteins are additionally able to bind to duplex RNA and have the potential to be functional in different oligomeric states.
authors.affiliation: Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schuetz
authors.affiliation: Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Murakawa
authors.affiliation: Structure and Membrane Interaction of G-Proteins, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenbaum
authors.affiliation: Laboratory for RNA Biology and Posttranscriptional Regulation, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Landthaler
authors.affiliation: 1] Helmholtz Protein Sample Production Facility, Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany [2] Chemistry and Biochemistry Institute, Freie Universität Berlin, 14195 Berlin, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Heinemann
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011061:Poly A / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics
chemical_list: C000592051:RC3H1 protein, human; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D011061:Poly A; D044767:Ubiquitin-Protein Ligases