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2Y95

Solution structure of AUCG tetraloop hairpin found in human Xist RNA A-repeats essential for X-inactivation

Summary for 2Y95
Entry DOI10.2210/pdb2y95/pdb
NMR InformationBMRB: 16714
Descriptor5'-R(*GP*GP*CP*GP*CP*AP*UP*CP*GP*GP*CP*GP*CP*C)-3' (1 entity in total)
Functional Keywordsrna, x chromosome inactivation, rna stemloop
Biological sourceHOMO SAPIENS (HUMAN)
Total number of polymer chains1
Total formula weight4492.74
Authors
Duszczyk, M.M.,Sattler, M. (deposition date: 2011-02-11, release date: 2011-10-26, Last modification date: 2024-06-19)
Primary citationDuszczyk, M.M.,Wutz, A.,Rybin, V.,Sattler, M.
The Xist RNA A-Repeat Comprises a Novel Aucg Tetraloop Fold and a Platform for Multimerization.
RNA, 17:1973-, 2011
Cited by
PubMed Abstract: X-chromosome inactivation (XCI) in female mammals depends on the noncoding RNA X inactivation specific transcript (Xist). The mechanism of chromosome-wide silencing by Xist is poorly understood. While it is established that the 5' region of Xist RNA, comprising the A-repeats and holding 7.5-8.5 copies of a conserved 26-mer sequence, is essential for Xist-mediated silencing, high-resolution structural information for the A-repeats is not available. Here, we report the three-dimensional solution structure of a 14-mer hairpin in the 5' region of a human A-repeat. This hairpin is remarkably stable and adopts a novel AUCG tetraloop fold, the integrity of which is required for silencing. We show that, contrary to previous predictions, the 3' region of single or tandem A-repeats mediates duplex formation in vitro. Significantly, mutations in this region disrupt the inter-repeat duplex formation in vitro and abrogate the silencing function of Xist A-repeats in vivo. Our data suggest that the complete A-repeat region may be stabilized by inter-repeat duplex formation and, as such, may provide a platform for multimerization and specific recognition of the AUCG tetraloops by trans-acting factors.
PubMed: 21947263
DOI: 10.1261/RNA.2747411
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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