Summary information and primary citation
- PDB-id
- 3nnc; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- RNA binding protein-RNA
- Method
- X-ray (2.2 Å)
- Summary
- Crystal structure of cugbp1 rrm1-2-RNA complex
- Reference
- Teplova M, Song J, Gaw HY, Teplov A, Patel DJ (2010): "Structural Insights into RNA Recognition by the Alternate-Splicing Regulator CUG-Binding Protein 1." Structure, 18, 1364-1377. doi: 10.1016/j.str.2010.06.018.
- Abstract
- CUG-binding protein 1 (CUGBP1) regulates multiple aspects of nuclear and cytoplasmic mRNA processing, with implications for onset of myotonic dystrophy. CUGBP1 harbors three RRM domains and preferentially targets UGU-rich mRNA elements. We describe crystal structures of CUGBP1 RRM1 and tandem RRM1/2 domains bound to RNAs containing tandem UGU(U/G) elements. Both RRM1 in RRM1-RNA and RRM2 in RRM1/2-RNA complexes use similar principles to target UGU(U/G) elements, with recognition mediated by face-to-edge stacking and water-mediated hydrogen-bonding networks. The UG step adopts a left-handed Z-RNA conformation, with the syn guanine recognized through Hoogsteen edge-protein backbone hydrogen-bonding interactions. NMR studies on the RRM1/2-RNA complex establish that both RRM domains target tandem UGUU motifs in solution, whereas filter-binding assays identify a preference for recognition of GU over AU or GC steps. We discuss the implications of CUGBP1-mediated targeting and sequestration of UGU(U/G) elements on pre-mRNA alternative-splicing regulation, translational regulation, and mRNA decay.
