Home > Funded Projects > Role of SNORD116/HBII-85 snoRNAs in Prader-Willi syndrome

Although the genetic region on chromosome 15 that is responsible for Prader-Willi Syndrome (PWS) has been known for many years, how the gene or genes within this large region cause the complex clinical features of PWS is still unknown. We have identified a small deletion on chromosome 15 of a patient with PWS features that narrows the causative region to a cluster of small genes of unknown function called SNORD116. SNORD116 are considered “orphans‟ because nothing is known about what they normally do or bind to. Using SNORD116 as “bait‟, we plan to “fish‟ for its interacting partners from mouse brain samples. We have shown that SNORD116 is highly expressed in the brain and have preliminary data indicating that fasting modulates this expression. With funding from FPWR, we plan to determine the normal biological role of SNORD116. Because obesity and hyperphagia are major features of PWS, we want to determine more about the SNORD116 expression changes when an animal is fasted and critically what happens to mice that don’t have Snord116; how do their brains respond to fasting?

RESEARCH OUTCOMES: We showed, using electrophoretic Mobility Shift Assays (EMSAs), that Snord116 does indeed bind to RNA. The attempts to isolate the RNA species however, proved technically challenging.  The initial approach we took assumed that Snord116, in its linear form, could bind to target RNA.  This may still be true, but the tools we used had too much inherent background noise.   More likely however, the binding of Snord116 to RNA is likely to require the entire small nucleolar ribonucleoprotein particle (snoRNP), which would not only contain RNA but also protein cofactors.  Our attempts at identifying such protein cofactors were more positive, but by no means conclusive.  More work will be required to identify individual protein species.

We have also identified a repertoire of genes that are differentially regulated between our patient with the microdeletion in the Snord116 region and family controls.  However, because we had only one patient with such a deletion, it is impossible to conclusively differentiate between biologically meaningful and stochastic differences.  Our ongoing experiments in identifying differentially regulated transcripts in the brains of mice with a targeted deletion should prove more informative, particular if there is overlap with the genes identified in our patient.

Funded Year:


Awarded to:

Giles Yeo, PhD




University of Cambridge