Document Detail


The Xist RNA A-repeat comprises a novel AUCG tetraloop fold and a platform for multimerization.
MedLine Citation:
PMID:  21947263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Malgorzata M Duszczyk; Anton Wutz; Vladimir Rybin; Michael Sattler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-26
Journal Detail:
Title:  RNA (New York, N.Y.)     Volume:  17     ISSN:  1469-9001     ISO Abbreviation:  RNA     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-18     Completed Date:  2011-11-25     Revised Date:  2014-02-24    
Medline Journal Info:
Nlm Unique ID:  9509184     Medline TA:  RNA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1973-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Dimerization
Humans
Models, Molecular
Nucleic Acid Conformation
RNA Folding*
RNA, Long Noncoding
RNA, Untranslated / chemistry*,  metabolism
Repetitive Sequences, Nucleic Acid*
Grant Support
ID/Acronym/Agency:
087530//Wellcome Trust; G0800784//Medical Research Council
Chemical
Reg. No./Substance:
0/RNA, Long Noncoding; 0/RNA, Untranslated; 0/XIST non-coding RNA
Comments/Corrections

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