Date of Award
12-2025
Degree Type
Honors College Thesis
Academic Program
Biological Sciences BS
Department
Biological Sciences
First Advisor
Kaitlin Baudier, Phd
Advisor Department
Biological Sciences
Abstract
Circular RNAs (circRNAs) are a class of ubiquitous eukaryotic RNAs created by back splicing. These noncoding RNAs can modulate gene expression and are implicated in aging and neurodegenerative diseases. To limit the contribution of circRNAs to aging and pathobiology, it is essential to understand how turnover of these molecules is regulated, as it is not clear which enzymes are chiefly responsible for degrading circRNAs in neurons. This study evaluates the roles of ribonucleases potentially involved in neural circRNA turnover using the model fly Drosophila melanogaster. A mifepristone-activated GAL4/UAS GeneSwitch expressed RNAi transgenes and inactivated the ribonucleases. Flies were evaluated on overall neural circRNA accumulation with RT-qPCR, biological fitness with climbing and lifespan assays, and neurodegenerative changes in brain morphology via immunofluorescence. Of the candidate enzymes that were assayed, the nuclear exoribonuclease RRP6 was affirmed to have the largest role in the regulation of circRNA levels in neurons. When this enzyme was depleted, the expression of genes linked to circRNA biogenesis was heavily upregulated, adult flies showed diminished motor activity, but no major morphological changes were observed. These results exhibited by this sublethal phenotype build on prior exosome studies by confirming RRP6's neural role in flies.
Copyright
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Recommended Citation
Serio, Joseph, "Neural RRP6 Depletion Drives circRNA Accumulation and Motor Impairment in Drosophila melanogaster Neurons" (2025). Honors Theses. 1069.
https://aquila.usm.edu/honors_theses/1069