Cellular role of MAGEL2 in Prader-Willi and Schaaf-Yang syndromes


PWS is caused by the loss of function of a set of genes. One of these genes, named MAGEL2, produces a protein that is important for the normal development of the brain, muscles and the endocrine system. Loss of function of MAGEL2 alone causes a disorder that is related to PWS, called Schaaf-Yang syndrome (SYS). To date, researchers have only studied the function of the second half of the MAGEL2 protein (called the “C” terminus), while the function of the first half of the protein (called the “N”-terminus) remains unknown. In this project, we will investigate the function of the MAGEL2 protein, to better understand the consequences of loss of function in PWS and SYS.

We recently discovered that the N-terminus of MAGEL2 protein interacts with a set of proteins important for the stability of mRNAs. mRNAs tell the cell what proteins to make. Some mRNAs give their instructions for protein production at the synapses of neurons. This is the cellular location where brain cells provide information to other brain cells and to muscles. We think that the N-terminal half of MAGEL2 binds to complexes that contain mRNAs, while the C-terminal half controls the stability of those complexes through a known function of MAGEL2 in protein ubiquitination. This activity is entirely missing in PWS. In SYS, the partial MAGEL2 protein can bind to mRNA containing complexes but not degrade them, which may be why SYS can be more severe than PWS.

Learn More!

Dr. Theresa Strong describes this grant, why we are excited about it and what the long term contributions of this project may be in our Research Grants Program Update Webinar, Spring 2018. You can learn more about this specific project in this video segment.

Research Outcomes: Public Summary

The MAGEL2 gene is inactivated in people with Prader-Willi syndrome, and mutations in MAGEL2 are found in people with Schaaf-Yang syndrome. This means that the MAGEL2 protein is either absent or malformed in these two disorders. Absence of a protein can affect with the may proteins act together in a pathway or in a protein complex. We found proteins that normally are very close to MAGEL2 in the cell, and so likely act together in a protein complex or a pathway. This information is invaluable to the design of therapeutics that may be able to replace the activity of the missing MAGEL2 protein in people with PWS.

Funded Year:


Awarded to:

Rachel Wevrick, PhD




The Governors of the University of Alberta


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