title: Structure of human Roquin-2 and its complex with constitutive-decay element RNA.
abstract: Roquin mediates mRNA degradation by recognizing the constitutive-decay element (CDE) in the 3' untranslated region of the target gene followed by recruitment of the deadenylation machinery. Deficiency or dysfunction of Roquin has been associated with autoimmunity and inflammation. To establish the structural basis for the recognition of CDE RNA by Roquin, the crystal structure of the ROQ domain of human Roquin-2 was determined in ligand-free and CDE-derived RNA-bound forms. The ROQ domain of Roquin-2 folded into a winged-helix structure in which the wing region showed structural flexibility and acted as a lid for RNA binding. The CDE RNA, forming a stem-loop structure, bound to the positively charged surface of the ROQ domain and was mainly recognized via direct interactions with the phosphate backbone in the 5' half of the stem-loop and its triloop and via indirect water-mediated interactions. Structural comparison with Roquin-1 revealed conserved features of the RNA-binding mode. Therefore, it is suggested that the Roquin proteins function redundantly in mRNA degradation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Sakurai
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Umeharu
authors.initials: U
authors.lastname: Ohto
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C000592051:RC3H1 protein, human; C000591671:RC3H2 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D012313:RNA; D044767:Ubiquitin-Protein Ligases
keywords: Roquin; mRNA degradation; stem-loop structure; winged-helix motif