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The Xist RNA A-repeat comprises a novel AUCG tetraloop fold and a platform for multimerization.
RNA 17, 1973-1982 (2011)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
X-inactivation; Xist RNA; A-repeats; nuclear magnetic resonance (NMR); structural biology; RNA tetraloop
Language
english
Publication Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
1355-8382
e-ISSN
1469-9001
Journal
RNA
Quellenangaben
Volume: 17,
Issue: 11,
Pages: 1973-1982
Publisher
Cold Spring Harbor Laboratory Press
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Structural Biology (STB)
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503000-001
PubMed ID
21947263
Scopus ID
80054719512
Erfassungsdatum
2011-11-09