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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2010-3-16
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pubmed:abstractText |
The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression units have been implicated as a cause for the Prader-Willi syndrome (PWS). We recently found that the C/D box snoRNA HBII-52 changes the alternative splicing of the serotonin receptor 2C pre-mRNA, which is different from the traditional C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1, PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of snoRNAs by RNase protection and northern blot analysis shows that the MBII-52 expressing unit generates shorter RNAs that originate from the full-length MBII-52 snoRNA through additional processing steps. These novel RNAs associate with hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data indicate that not a traditional C/D box snoRNA MBII-52, but a processed version lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This processed snoRNA functions in alternative splice-site selection. Its substitution could be a therapeutic principle for PWS.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1460-2083
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1153-64
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pubmed:dateRevised |
2011-7-27
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pubmed:meshHeading |
pubmed-meshheading:20053671-Alternative Splicing,
pubmed-meshheading:20053671-Animals,
pubmed-meshheading:20053671-Gene Expression Regulation,
pubmed-meshheading:20053671-Heterogeneous-Nuclear Ribonucleoproteins,
pubmed-meshheading:20053671-Mice,
pubmed-meshheading:20053671-Prader-Willi Syndrome,
pubmed-meshheading:20053671-RNA, Small Nucleolar,
pubmed-meshheading:20053671-RNA Editing,
pubmed-meshheading:20053671-RNA Precursors,
pubmed-meshheading:20053671-Receptor, Serotonin, 5-HT2C
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pubmed:year |
2010
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pubmed:articleTitle |
The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing.
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pubmed:affiliation |
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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