7po6

Xist (m6A)UCG tetraloop RNA bound to the YTH domain of YTHDC1

spinqualitylabelsall models 7po6, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7po6 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.77Å Ligands: 6MZ, EDO, GTP, NA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function YTDC1_HUMAN RNA-binding protein that regulates alternative splice site selection. Publication Abstract from PubMed The A-repeat region of the lncRNA Xist is critical for X inactivation and harbors several N6-methyladenosine (m6A) modifications. How the m6A modification affects the conformation of the conserved AUCG tetraloop hairpin of the A-repeats and how it can be recognized by the YTHDC1 reader protein is unknown. Here, we report the NMR solution structure of the (m6A)UCG hairpin, which reveals that the m6A base extends 5' stacking of the A-form helical stem, resembling the unmethylated AUCG tetraloop. A crystal structure of YTHDC1 bound to the (m6A)UCG tetraloop shows that the (m6A)UC nucleotides are recognized by the YTH domain of YTHDC1 in a single-stranded conformation. The m6A base inserts into the aromatic cage and the U and C bases interact with a flanking charged surface region, resembling the recognition of single-stranded m6A RNA ligands. Notably, NMR and fluorescence quenching experiments show that the binding requires local unfolding of the upper stem region of the (m6A)UCG hairpin. Our data show that m6A can be readily accommodated in hairpin loop regions, but recognition by YTH readers requires local unfolding of flanking stem regions. This suggests how m6A modifications may regulate lncRNA function by modulating RNA structure. Structural effects of m6A modification of the Xist A-repeat AUCG tetraloop and its recognition by YTHDC1.,Jones AN, Tikhaia E, Mourao A, Sattler M Nucleic Acids Res. 2022 Feb 28;50(4):2350-2362. doi: 10.1093/nar/gkac080. PMID:35166835 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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