SNORD116 and SNORD115 change expression of multiple genes and modify each other's activity

Area of Science:

• Genetics
• Molecular Biology
• Neuroscience

Background:

• Prader-Willi syndrome (PWS), a common cause of human obesity, is linked to the loss of SNORD115 and SNORD116 gene clusters.
• These orphan C/D box small nucleolar RNAs (snoRNAs) do not target ribosomal RNAs or small nuclear RNAs, distinguishing them from canonical snoRNAs.

Purpose of the Study:

• To identify the molecular targets and functions of SNORD115 and SNORD116.
• To investigate the interplay between SNORD115 and SNORD116 in regulating gene expression.
• To explore the role of these snoRNAs in the pathophysiology of Prader-Willi syndrome.

Main Methods:

• Genome-wide array analysis was performed in HEK 293T cells overexpressing SNORD115 and SNORD116, individually and together.
• Gene expression profiling was conducted on post-mortem hypothalamic samples from individuals with PWS and age-matched controls.

Main Results:

• SNORD116 overexpression altered the expression of over 200 genes, primarily affecting mRNA levels.
• SNORD115 was found to modify the gene expression effects of SNORD116.
• Analysis of PWS hypothalami identified 23 genes whose expression levels were influenced by SNORD116.

Conclusions:

• SNORD115 and SNORD116 are key regulators of multiple gene expression pathways.
• These two snoRNAs exhibit a mutual regulatory interaction, influencing each other's activity.
• The findings provide insights into the molecular mechanisms underlying Prader-Willi syndrome and obesity.