4QI2

X-ray structure of the ROQ domain from murine Roquin-1 in complex with a 23-mer Tnf-CDE RNA

Summary for 4QI2

• Entry DOI: 10.2210/pdb4qi2/pdb
• Related: 4QI0
• Descriptor: Roquin-1, RNA (5'-R(*AP*CP*AP*UP*GP*UP*UP*UP*UP*CP*UP*GP*UP*GP*AP*AP*AP*AP*CP*GP*GP*AP*G)-3') (3 entities in total)
• Functional Keywords: roq domain, winged-helix domain, rna binding, tnf cde rna, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm, P-body: Q4VGL6
• Total number of polymer chains: 8
• Total formula weight: 111671.94

Authors

Janowski, R.,Schlundt, A.,Sattler, M.,Niessing, D. (deposition date: 2014-05-30, release date: 2014-07-16, Last modification date: 2023-09-20)

Primary citation

Schlundt, A.,Heinz, G.A.,Janowski, R.,Geerlof, A.,Stehle, R.,Heissmeyer, V.,Niessing, D.,Sattler, M.
Structural basis for RNA recognition in roquin-mediated post-transcriptional gene regulation.
Nat.Struct.Mol.Biol., 21:671-678, 2014

PubMed Abstract: 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.

PubMed: 25026077
DOI: 10.1038/nsmb.2855

Experimental method

X-RAY DIFFRACTION (3 Å)