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The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing

Kishore, S. and Khanna, A. and Zhang, Z. and Hui, J. and Balwierz, P. J. and Stefan, M. and Beach, C. and Nicholls, R. D. and Zavolan, M. and Stamm, S.. (2010) The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Human molecular genetics, Vol. 19, H. 7. pp. 1153-1164.

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Official URL: http://edoc.unibas.ch/dok/A5842486

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Abstract

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 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford Univ. Press
ISSN:0964-6906
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 07:17
Deposited On:14 Sep 2012 06:38

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