Examination of Snord116 in Neuronal Ribosome Biology

About This Grant

PROJECT SUMMARY The proposed project aims to elucidate the neuron-specific mechanisms by which SNORD116 loss contributes to Prader-Willi syndrome, a complex neurodevelopmental disorder. We seek to comprehensively characterize the role of SNORD116 in ribosome biogenesis and translation in neurons using advanced high-throughput sequencing techniques like chimeric eCLIP and ribosome sequencing. Preliminary data indicate that Snord116 interacts with rRNA and a neuron-specific homologue of the methyltransferase Fibrillarin, FBLL1, suggesting that Snord116 may act as a ribosome biogenesis factor to meet the unique translation demands of neurons. By testing the consequences of these interactions, we aim to fill a critical gap in understanding Prader-Willi syndrome pathogenesis. Our objectives are to (1) determine the role of Snord116 in ribosome biogenesis, (2) assess the effect of Snord116 loss on neuronal protein synthesis, and (3) explore co-factors like FBLL1 that may modulate its function. Investigating these early molecular events could open possible avenues for correcting the distinctive growth and neurobehavioral features of Prader-Willi syndrome and offer broader insights into other neurodevelopmental disorders.