Lay Abstract
A cluster of small nucleolar RNAs (snoRNAs), known as the SNORD116 cluster, appears to be of critical importance in Prader-Willi syndrome (PWS). However, despite over two decades of extensive investigation, a direct interaction between SNORD116 and a predicted target has yet to be shown, and as such the mechanism behind PWS remains unknown.
Our pilot data employed a new approach that exploited differences in species, tissue, and model system to identify a direct target candidate (PKP1). PKP1 is a key component of a crucial signaling hub (known as the desmosome), which can regulate cell behaviour during development and disease. In this proposal we aim to build on this pilot data to confirm if PKP1 is a direct target of SNORD116. To do this we will use SNORD116-knockout human stem cell lines to define PKP1 signalling during neuronal development and determine whether SNORD116 plays a role in regulating this.
Confirming the first direct target of SNORD116 would significantly advance our understanding of the molecular mechanism of PWS. This would open a new field of investigation, in which drugs targeting desmosome proteins and downstream signaling pathways could lead to improved PWS treatment. This perfectly aligns with the mission of FPWR, specifically advancing our gene to observable characteristic understanding.
Funded Year:
2025
Awarded to:
James Smith, Ph.D.
Amount:
$83,259
Institution:
University of East Anglia
Researcher:
James Smith, PhD
