snoRNAs linked to Prader-Willi Syndrome

Small nucleolar RNAs (snoRNAs) have never before been implicated in alternative splicing. Stefan Stamm and Shivendra Kishore, of the Friedrich-Alexander University Institute for Biochemistry, suggest that HBII-52, a non-coding RNA located on chromosome 15 regulates alternative splicing of the serotonin receptor 2C located on the X chromosome.1 The snoRNA locus is maternally imprinted, and loss of paternal expression results in Prader-Willi Syndrome, a congenital disease

Mar 1, 2006
The Scientist Staff

Small nucleolar RNAs (snoRNAs) have never before been implicated in alternative splicing. Stefan Stamm and Shivendra Kishore, of the Friedrich-Alexander University Institute for Biochemistry, suggest that HBII-52, a non-coding RNA located on chromosome 15 regulates alternative splicing of the serotonin receptor 2C located on the X chromosome.1 The snoRNA locus is maternally imprinted, and loss of paternal expression results in Prader-Willi Syndrome, a congenital disease characterized by developmental and neurological defects.

Tom Blumenthal, chair of biochemistry and molecular genetics at the University of Colorado Health Sciences Center, says, "This one just struck me as really novel."

"This is in fact a very interesting case of alternative splicing because it means the difference between making a functional and a non-functional serotonin receptor. So, it is by its nature a very interesting case of alternative splicing and it turns out to be regulated by what appears to me to be an entirely novel mechanism."

"Normally a silencer binds to the pre-mRNA preventing use of a specific splice site. This snoRNA comes in there and binds instead, preventing the silencer from binding. Therefore, the splice site gets utilized.

"That's really only part of the story. Because Prader-Willi patients don't splice the serotonin receptor properly, it's perfectly reasonable to think that that gives the phenotype. That makes it doubly interesting, I think."

References

1. S. Kishore, S. Stamm "The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C," Science, 311:230-2, Jan. 13, 2006.