Novel functions and translation mechanisms involving SNURF and neural-specific SmN spliceosomal protein

Funding Summary

One of the major genes in the PWS critical region, SNURF-SNRPN, is relatively understudied. Here, Dr. McManus will use cell models of human brain, pancreas and heart to understand the function of the proteins that this gene produces.

Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.

Lay Abstract

The goals of this proposal are to determine the functions of the SNURF-SNRPN gene and identify how the SNURF and SNRPN proteins are produced. The SNURF-SNRPN gene is deleted or inactivated in nearly all patients with PWS, and some patients have been reported with localized errors specifically in this gene. Since its discovery, it has been suspected that loss of the SNURF-SNRPN gene contributes to PWS. However, the normal purposes of the two proteins produced from this gene are poorly understood. Indeed, it is not clear even how the SNURF and SNRPN proteins are produced. While nearly all human genes each produce a single protein, SNURF-SNRPN produces two. Our research suggests that a small part of the gene helps control how much of each protein is made and may also regulate the production of each protein in response to cell stress. We proposed new research to study how the SNURF and SNRPN proteins are produced and regulated in laboratory cells that mimic the human brain, heart, and pancreas, which are the tissues that produce the highest levels of PWS-gene products. We will also carry out experiments to learn what the SNURF and SNRPN proteins do in these cells. We suspect SNRPN influences the production of proteins from many other genes. To find such genes, we will delete SNRPN in laboratory cells and measure the types and amounts of proteins expressed from all other genes. Because much less is known about SNURF, we will use new tools to find the proteins that bind the SNURF protein in laboratory cells to provide insight into how SNURF functions. These studies will help us better understand PWS, by learning about the production and roles of these two important proteins produced from the SNURF-SNRPN gene in critical tissues relevant to PWS.