| The Xist RNA A-repeat comprises a novel AUCG tetraloop fold and a platform for multimerization. | |
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MedLine Citation:
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PMID: 21947263 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Malgorzata M Duszczyk; Anton Wutz; Vladimir Rybin; Michael Sattler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-09-26 |
Journal Detail:
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Title: RNA (New York, N.Y.) Volume: 17 ISSN: 1469-9001 ISO Abbreviation: RNA Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-18 Completed Date: 2011-11-25 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 9509184 Medline TA: RNA Country: United States |
Other Details:
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Languages: eng Pagination: 1973-82 Citation Subset: IM |
Affiliation:
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Institute of Structural Biology, Helmholtz Zentrum München, 85764 Neuherberg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Dimerization Humans Models, Molecular Nucleic Acid Conformation RNA Folding* RNA, Long Untranslated RNA, Untranslated / chemistry*, metabolism Repetitive Sequences, Nucleic Acid* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Long Untranslated; 0/RNA, Untranslated; 0/XIST non-coding RNA |
| Comments/Corrections | |
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