Transcriptome-wide identification and functional annotation of PWS-encoded SNORD targets

Funding Summary

The SNORD genes are known to be very important in PWS, but there is a lack of appropriate tools to study the target and function of these genes. Dr. He and his team have developed two new methods that can map the targets of the SNORD genes. They will apply these new methods to mouse models and human cell lines with a deficiency in PWS-encoded SNORDs to better understand the function of the SNORD genes and help us understand how loss of these genes leads to the characteristics of PWS. 

Lay Abstract

The minimal gene responsible for the phenotype of Prader-Willi syndrome (PWS) has been mapped to a cluster of imprinted box C/D small nucleolar RNA (SNORD) genes, but the targets and function of these PWS-encoded SNORDs have been elusive largely due to the lack of enabling tools to study them. The classical function of SNORDs is to bind and install sequence-specific 2’-O-methylation (Nm) on their target RNAs. To find out the target RNAs of PWS-encoded SNORDs and the Nm sites that they install, methods to effectively map RNA-RNA interactions and Nm modifications are required. We have recently developed two new methods that can map RNA-RNA interactions and Nm modification at the whole transcriptome level. We will apply our new methods on mouse models and human cell lines with a deficiency in PWS-encoded SNORDs. These studies will lay the foundation for further mechanistic investigations of SNORD functions in PWS at the transcriptomic scale, and will significantly advance our understanding of PWS pathophysiology.