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

@article{Kishore2006TheSH,
  title={The snoRNA HBII-52 Regulates Alternative Splicing of the Serotonin Receptor 2C},
  author={Shivendra Kishore and Stefan Stamm},
  journal={Science},
  year={2006},
  volume={311},
  pages={230 - 232}
}
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… 
View on AAAS
ncbi.nlm.nih.gov
649 Citations
Highly Influential Citations
23
Background Citations
254
Methods Citations
10
Results Citations
2

649 Citations

Role of Alternative Splicing of the 5-HT 2C Receptor in the Prader–Willi Syndrome

The regulation of alternative splicing of exon Vb of the 5-HT2C receptor appears to be altered in the Prader–Willi syndrome (PWS), and the exon encodes the second intracellular loop that is important for signaling.

Regulation of alternative splicing by snoRNAs.

The SNURF-SNRPN locus located on chromosome 15 is maternally imprinted and generates a large transcript containing at least 148 exons, which could contribute to the disease.

Differential regulation of non-protein coding RNAs from Prader-Willi Syndrome locus

Prader-Willi Syndrome (PWS) is a neurogenetic disorder caused by the deletion of imprinted genes on the paternally inherited human chromosome 15q11-q13. This locus harbours a long non-protein-coding…

Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster

A microdeletion of the HBII-85 snoRNAs in a child with PWS provides, in combination with previous data, effectively conclusive evidence that deficiency of HBOs causes the key characteristics of the PWS phenotype, although some atypical features suggest that other genes in the region may make more subtle phenotypic contributions.

Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour.

The physiological consequences of altered RNA editing of 5htr2c linked to mbii-52 loss that may underlie specific aspects of the complex PWS phenotype are illustrated and point to an important functional role for this imprinted snoRNA.

Role of Alternative Splicing of the Serotonin Receptor 2 C in the Prader – Willi Syndrome

The 5-HT 2C receptor pre-messenger ribonucleic acid (pre-mRNA) undergoes both editing and alternative pre-mRNA splicing. Both events occur in the cell nucleous and are summarized below. RNA editing…

Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader–Willi syndrome

Alternative Splicing and Extensive RNA Editing of Human TPH2 Transcripts

Results strongly suggest a complex fine-tuning of central nervous system 5-HT biosynthesis by TPH2 alternative splicing and RNA editing, involved in the etiology of psychiatric diseases, such as suicidal behaviour.

The posterior pituitary expresses the serotonin receptor 2C

Molecular evolution of the HBII-52 snoRNA cluster.

...

References

SHOWING 1-10 OF 16 REFERENCES

Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization.

Three C/D-box small nucleolar RNAs (snoRNAs) and one H/ACA-box snoRNA in mouse and human are identified, demonstrating their paternal imprinting status and pointing to their potential role in the etiology of PWS.

Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene.

Using in vitro editing, a novel editing site (F) is identified located in the intronic part of the stem-loop and demonstrated editing at this site in human brain, which suggests an important novel role for RNA editing.

Imprinting in Prader-Willi and Angelman syndromes.

Regulation of serotonin-2C receptor G-protein coupling by RNA editing

Observations indicate that RNA editing is a new mechanism for regulating serotonergic signal transduction and suggest that this post-transcriptional modification may be critical for modulating the different cellular functions that are mediated by other members of the G-protein-coupled receptor superfamily.

Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin2C Receptors

Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites, and identifies a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein‐coupling activity.

Regulation of the neuron-specific exon of clathrin light chain B.

Essential nucleotides direct neuron-specific splicing of gamma 2 pre-mRNA.

The regulated splicing of rat gamma 2 pre-mRNA is investigated as a step toward understanding the molecular basis of a neuron-specific splicing event involving cassette exon selection, and essential nucleotides in the exon and 3' splice site region defined in this study are novel.

The in vivo minigene approach to analyze tissue-specific splicing.

Systematic Identification and Analysis of Exonic Splicing Silencers

ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs

This work shows that ADAR2- but not ADAR1-mediated RNA editing occurs in the nucleolus, and identifies a brain-specific small RNA, termed MBII-52, which was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2′-O-methylation.