Organization of Snornas in the Prader Willi Critical Region

The HBII-52 snoRNA resides in the SNURF-SNRPN locus (for small RNP in neurons [SmN] upstream reading frame). The SNURF-SNRPN locus whose loss of expression causes PWS spans more than 460 kb and contains at least 148 exons (Runte et al. 2001) (Fig. 21.3a). The locus is maternally imprinted, meaning that only the allele from the father is expressed. The loss of expression from this paternal allele, most frequently through genomic deletions causes PWS. The SNURF-SNRPN locus has a complex architecture. Ten exons in the 5' part of the gene are transcribed into a bicistronic mRNA that encodes the SNURF (SmN upstream reading frame) and the SmN (small RNP in Neurons) protein. Adjacent to the SNURF-SNRPN gene is a bipartite imprinting center (IC) that silences most maternal genes of the PWS critical region. The large 3' UTR region of the SNURF-SNRPN gene harbors clusters of the C/D box snoRNAs HBII-85 and HBII-52 that are present in at least 24 and 47 copies, respectively. In addition, the region harbors single copies of other C/D box snoRNAs: HBII-13, HBII-436, HBII-437 HBII-438A, and HBII-438B. The snoRNAs are flanked by noncoding exons and show a large degree of conservation between mammalian species. Their flanking, noncoding exons are only poorly conserved, suggesting that the snoRNAs are important, not the flanking exons (Fig. 21.3a). The snoRNAs in this locus show a tissue-specific expression. Expression of HBII-52 could be detected only in brain, whereas other snoRNAs are expressed also in nonbrain tissues (reviewed in Kishore and Stamm 2006b). A link between PWS and snoRNAs was supported by the recent finding that a microdele-tion containing only snoRNAs, including all the HBII-85 and most of the HBII-52 cluster leads to the PWS phenotype (Sahoo et al. 2008) (Fig. 21.3a). The accumulated data strongly suggest that the loss of snoRNA expression from the SNURF-SNRNP region plays a decisive role in PWS.

Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

Get My Free Ebook


Post a comment