DOI
https://doi.org/10.25772/XBHY-2111
Defense Date
2015
Document Type
Thesis
Degree Name
Master of Science
Department
Human Genetics
First Advisor
Dr. Rita Shiang
Second Advisor
Dr. Paul Fisher
Third Advisor
Dr. Andrew Davies
Abstract
The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction..
PNPase is also known to transport small RNAs into the mitochondria which in turn can affect mitochondria RNA splicing and translation of proteins involved in respiration. Further investigation showed a significant accumulation of polycistronic mitochondrial transcripts in knockdown animals. Lastly, this model has shown that PNPase knockdown is functionally comparable across species and is a viable model for future studies.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-5-2015