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Science 311 (5758): 230-232

Copyright © 2006 by the American Association for the Advancement of Science

The snoRNA HBII-52 Regulates Alternative Splicing of the Serotonin Receptor 2C

Shivendra Kishore, and Stefan Stamm*

Abstract: The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15. This region contains a small nucleolar RNA (snoRNA), HBII-52, that exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin receptor 5-HT2CR. We found that HBII-52 regulates alternative splicing of 5-HT2CR by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different 5-HT2CR messenger RNA (mRNA) isoforms than healthy individuals. Our results show that a snoRNA regulates the processing of an mRNA expressed from a gene located on a different chromosome, and the results indicate that a defect in pre-mRNA processing contributes to the Prader-Willi syndrome.

Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, Fahrstraße 17, 91054 Erlangen, Germany.

* To whom correspondence should be addressed. E-mail: stefan{at}stamms-lab.net

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   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis.
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   Abstract »    Full Text »    PDF »
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M. F. Mehler and J. S. Mattick (2007)
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   Abstract »    Full Text »    PDF »
Origin of phenotypes: Genes and transcripts.
T. R. Gingeras (2007)
Genome Res. 17, 682-690
   Abstract »    Full Text »    PDF »
A new paradigm for developmental biology.
J. S. Mattick (2007)
J. Exp. Biol. 210, 1526-1547
   Abstract »    Full Text »    PDF »
The implications of alternative splicing in the ENCODE protein complement.
M. L. Tress, P. L. Martelli, A. Frankish, G. A. Reeves, J. J. Wesselink, C. Yeats, P. l. Olason, M. Albrecht, H. Hegyi, A. Giorgetti, et al. (2007)
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   Abstract »    Full Text »    PDF »
New bioinformatic tools for analysis of nucleotide modifications in eukaryotic rRNA.
D. Piekna-Przybylska, W. A. Decatur, and M. J. Fournier (2007)
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   Abstract »    Full Text »    PDF »
RNAdb 2.0--an expanded database of mammalian non-coding RNAs.
K. C. Pang, S. Stephen, M. E. Dinger, P. G. Engstrom, B. Lenhard, and J. S. Mattick (2007)
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   Abstract »    Full Text »    PDF »
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J.-H. Yang, X.-C. Zhang, Z.-P. Huang, H. Zhou, M.-B. Huang, S. Zhang, Y.-Q. Chen, and L.-H. Qu (2006)
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   Abstract »    Full Text »    PDF »
Non-coding RNAs in the nervous system.
M. F. Mehler and J. S. Mattick (2006)
J. Physiol. 575, 333-341
   Abstract »    Full Text »    PDF »
Defective splicing, disease and therapy: searching for master checkpoints in exon definition.
E. Buratti, M. Baralle, and F. E. Baralle (2006)
Nucleic Acids Res. 34, 3494-3510
   Abstract »    Full Text »    PDF »
Non-coding RNA.
J. S. Mattick and I. V. Makunin (2006)
Hum. Mol. Genet. 15, R17-R29
   Abstract »    Full Text »    PDF »
Regulation of Alternative Splicing by snoRNAs.
S. KISHORE and S. STAMM (2006)
Cold Spring Harb Symp Quant Biol 71, 329-334
   Abstract »    PDF »
The Expanding Universe of Noncoding RNAs.
G.J. HANNON, F.V. RIVAS, E.P. MURCHISON, and J.A. STEITZ (2006)
Cold Spring Harb Symp Quant Biol 71, 551-564
   Abstract »    PDF »
Evolution of small nucleolar RNAs in nematodes..
A. Zemann, A. op de Bekke, M. Kiefmann, J. Brosius, and J. Schmitz (2006)
Nucleic Acids Res. 34, 2676-2685
   Abstract »    Full Text »    PDF »

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