Research Notes: Genes - SNORD115-1
(small nucleolar RNA, C/D box 115-1)

• paternally imprinted
• EntrezGene | OMIM
• aka RNHBII52; HBII-52-1
• snoRNA

From OMIM:

• Northern blot analysis detected expression of HBII-52 in human brain, but not in liver, muscle, lung, kidney, and heart. Cavaille et al. (2000) determined that HBII-52 maps to an imprinted region of chromosome 15 associated with Angelman syndrome (AS; 105830) and Prader-Willi syndrome (PWS; 176270). They concluded that HBII-52 is a paternally imprinted gene, since it was expressed in cortex RNA from a normal control brain and from an AS patient with a maternally inherited deletion, but was absent from cortex RNA from a PWS patient with a paternally inherited deletion and from a mouse model of PWS.
• Cavaille et al. (2000) identified an 18-nucleotide phylogenetically conserved region in HBII-52 complementary to a critical segment of the serotonin-2C receptor mRNA (HTR2C; 312861), suggesting that HBII-52 may have a role in processing HTR2C mRNA.
• The snoRNA HBII-52 is contained within the Prader-Willi deleted region on chromosome 15q11 and exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin receptor HTR2C. Kishore and Stamm (2006) found that HBII-52 regulates alternative splicing of HTR2C by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different HTR2C mRNA isoforms than healthy individuals. Kishore and Stamm (2006) concluded 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.
• By genomic sequence analysis, Cavaille et al. (2000) identified 47 tandem copies of the HBII-52 gene on chromosome 15q11-q13. The HBII-52 copies are slightly divergent units of about 1.9 kb regularly spaced within a stretch of 99 kb.
• Runte et al. (2001) determined that HBII-52 and several other snoRNAs are encoded within intronic segments of the SNURF-SNRPN (182279) transcript. HBII-52 is located within introns between exons 63 and 144 of SNURF-SNRPN.
• Runte et al. (2005) found that individuals with complete deletion of all copies of HBII-52 had no obvious clinical phenotype, suggesting that HBII-52 does not play a major role in PWS.
• Sato et al. (2007) reported a Japanese family in which a boy with AS and his asymptomatic mother and maternal grandfather all had a 1,487-kb deletion on chromosome 15, encompassing HBII-52. The mother was evaluated with regard to diagnostic criteria for PWS but the diagnosis was considered unlikely, suggesting that HBII-52 may not be important in the pathogenesis of PWS.

Science. 2006 Jan 13.
The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C.
Kishore S, Stamm S.
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, Fahrstrasse 17, Erlangen, Germany.
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-HT(2C)R. We found that HBII-52 regulates alternative splicing of 5-HT(2C)R by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different 5-HT(2C)R 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.

Hum Genet. 2005 Feb.
Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome.
Runte M, Varon R, Horn D, Horsthemke B, Buiting K.
Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, Essen, Germany.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurogenetic disorders caused by the loss of function of imprinted genes in 15q11-q13. The maternally expressed UBE3A gene is affected in AS. Four protein-encoding genes (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438A, HBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear. To examine the role of the HBII-52 snoRNA genes, we have reinvestigated an AS family with a submicroscopic deletion spanning UBE3A and flanking sequences. By fine mapping of the centromeric deletion breakpoint in this family, we have found that the deletion affects all of the 47 HBII-52 genes. Since the complete loss of the HBII-52 genes in family members who carry the deletion on their paternal chromosome is not associated with an obvious clinical phenotype, we conclude that HBII-52 snoRNA genes do not play a major role in PWS. However, we cannot exclude the possibility that the loss of HBII-52 has a phenotypic effect when accompanied by the loss of function of other genes in 15q11-q13.