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.

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