| First Author | Schlundt A | Year | 2014 |
| Journal | Nat Struct Mol Biol | Volume | 21 |
| Issue | 8 | Pages | 671-8 |
| PubMed ID | 25026077 | Mgi Jnum | J:261058 |
| Mgi Id | MGI:6154479 | Doi | 10.1038/nsmb.2855 |
| Citation | Schlundt A, et al. (2014) Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation. Nat Struct Mol Biol 21(8):671-8 |
| abstractText | Roquin function in T cells is essential for the prevention of autoimmune disease. Roquin interacts with the 3'' untranslated regions (UTRs) of co-stimulatory receptors and controls T-cell activation and differentiation. Here we show that the N-terminal ROQ domain from mouse roquin adopts an extended winged-helix (WH) fold, which is sufficient for binding to the constitutive decay element (CDE) in the Tnf 3'' UTR. The crystal structure of the ROQ domain in complex with a prototypical CDE RNA stem-loop reveals tight recognition of the RNA stem and its triloop. Surprisingly, roquin uses mainly non-sequence-specific contacts to the RNA, thus suggesting a relaxed CDE consensus and implicating a broader spectrum of target mRNAs than previously anticipated. Consistently with this, NMR and binding experiments with CDE-like stem-loops together with cell-based assays confirm roquin-dependent regulation of relaxed CDE consensus motifs in natural 3'' UTRs. |
