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Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40.
Nat. Commun. 7:11032 (2016)
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 3'-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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Costimulator Messenger-rna; Constitutive-decay Element; Helper T-cells; Nmr-spectroscopy; Binding Proteins; Differentiation; Autoimmunity; Regnase-1; Family; Inflammation
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
Zeitschrift
Nature Communications
Quellenangaben
Band: 7,
Artikelnummer: 11032
Verlag
Nature Publishing Group
Verlagsort
London
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed