First Author | Janowski R | Year | 2016 |
Journal | Nat Commun | Volume | 7 |
Pages | 11032 | PubMed ID | 27010430 |
Mgi Jnum | J:236832 | Mgi Id | MGI:5807332 |
Doi | 10.1038/ncomms11032 | Citation | Janowski R, et al. (2016) Roquin recognizes a non-canonical hexaloop structure in the 3'-UTR of Ox40. Nat Commun 7:11032 |
abstractText | 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. |