Cold Spring Harb Symp Quant Biol. 2006;71:329-34.
Regulation of alternative splicing by snoRNAs.
Kishore S, Stamm S.
University of Erlangen, Institute for Biochemistry, Erlangen, Germany.

The SNURF-SNRPN locus located on chromosome 15 is maternally imprinted and generates a large transcript containing at least 148 exons. Loss of the paternal allele causes Prader-Willi syndrome (PWS). The 3' end of the transcript harbors several evolutionarily conserved C/D box small nucleolar RNAs (snoRNAs) that are tissue-specifically expressed. With the exception of 47 copies of HBII-52 snoRNAs, none of the snoRNAs exhibit complementarity to known RNAs. Due to an 18-nucleotide sequence complementarity, HBII-52 can bind to the alternatively spliced exon Vb of the serotonin receptor 2C pre-mRNA, where it masks a splicing silencer, which results in alternative exon usage. This silencer can also be destroyed by RNA editing, which changes the amino acid sequence and appears to be independent of HBII-52. Lack of HBII-52 expression in individuals with PWS causes most likely a lack of the high-efficacy serotonin receptor, which could contribute to the disease. It is therefore possible that snoRNAs could act as versatile modulators of gene expression by modulating alternative splicing.

Categories: 2006, PWS, PWS genes, Gene expression, RNA processing, snoRNAs, SNURF, SNRPN, HBII-52, Serotonin