Grant: Project Grant

While many genes coding for proteins have been extensively studied, the role of noncoding RNA (ncRNA) genes is less well-understood. Unlike coding genes, ncRNA genes do not code for proteins but produce ncRNAs which perform diverse functions under their RNA form. NcRNAs include small nucleolar RNAs (snoRNAs), a large family present in all multicellular organisms and beyond. In the human genome, most snoRNAs are located in other longer genes referred to as their host genes. SnoRNAs are best characterized for their role in the production of ribosomes, the cellular machinery responsible for protein production. However, in recent years, snoRNAs have also been implicated in multiple levels of gene expression regulation, suggesting roles as master regulators. Using validated examples of snoRNA targets, we have recently created an accurate predictor of snoRNA interactors using artificial intelligence. The analysis of these predictions led to the identification of snoRNAs regulating in similar ways messenger RNAs involved in common pathways, and often overlapping binding sites of specific proteins. In addition, we also discovered snoRNAs regulating the transcripts of their host genes. To better understand the role of snoRNA complexes in the regulation of gene expression, we will rank snoRNA-mRNA interactions and snoRNA-protein interactions to identify the most likely snoRNA-protein regulating complexes and characterize their molecular functions and mechanisms of action. We will then disrupt the expression and mutate snoRNAs of interest to characterize their effects on their targets and their involvement in cellular function. Importantly, snoRNAs and their targets are often found strongly deregulated in diverse cancers, but we do not understand why. This study will build the foundation to unravel snoRNA involvement in cancer and devise ways to harness this knowledge for earlier detection and complementary treatment strategies.