Roquin recognizes a non-canonical hexaloop structure in the 3 '-UTR of Ox40

Janowski, Robert; Heinz, Gitta A.; Schlundt, Andreas; Wommelsdorf, Nina; Brenner, Sven; Gruber, Andreas R.; Blank, Michael; Buch, Thorsten; Buhmann, Raymund; Zavolan, Mihaela; Niessing, Dierk; Heissmeyer, Vigo und Sattler, Michael (2016): Roquin recognizes a non-canonical hexaloop structure in the 3 '-UTR of Ox40. In: Nature Communications, Bd. 7, 11032

Abstract

The RNA-binding protein Roquin is required to prevent autoimmunity. Roquin controls T-helper cell activation and differentiation by limiting the induced expression of costimulatory receptors such as tumor necrosis factor receptor superfamily 4 (Tnfrs4 or Ox40). A constitutive decay element (CDE) with a characteristic triloop hairpin was previously shown to be recognized by Roquin. Here we use SELEX assays to identify a novel U-rich hexaloop motif, representing an alternative decay element (ADE). Crystal structures and NMR data show that the Roquin-1 ROQ domain recognizes hexaloops in the SELEX-derived ADE and in an ADE-like variant present in the Ox40 30-UTR with identical binding modes. In cells, ADE-like and CDE-like motifs cooperate in the repression of Ox40 by Roquin. Our data reveal an unexpected recognition of hexaloop cis elements for the posttranscriptional regulation of target messenger RNAs by Roquin.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Immunologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2041-1723
• Sprache: Englisch