Year: 2009
Type: dissertation
Abstract: Small RNA-mediated gene silencing is an ancient, evolutionarily conserved and only recently discovered gene regulatory mechanism.This thesis is aimed towards understanding the function of small RNA pathways in the model organism Caenorhabditis elegans, and furthermore to understand their role in neurodegenerative diseases.In order to study small RNA pathways and their potential therapeutic applications in neurological diseases, molecular genetic, RNA interference, microarray, and in silico techniques were used as an experimental approach.Firstly, different neuron types were examined for their sensitivity to exogenously delivered small interfering RNAs (exo-siRNAs).The sensitivity was found to vary between different neuron types and dysfunctional RRF-3 protein was shown to increase the effectiveness in all measured cell types.Secondly, using an rrf-3 mutant animal, candidate targets of endogenous small interfering RNAs (endo-siRNAs) were identified and their functions were found to be enriched in regulating genes involved in protein phosphorylation, embryonic development, and sperm motility.Thirdly, endogenous siRNAs previously identified by high-throughput sequencing were distributed by size and found to have size-specific functions.Finally, expression levels of microRNAs in several C. elegans models of Parkinson's disease were measured and two differentially regulated microRNA families were identified as potentially involved in Parkinson's disease-associated pathogenic mechanisms.In conclusion, the effectiveness and functions of exogenous and endogenous small RNAs were studied in order to provide a more thorough understanding of their biology with the prospect of using this information in development of small RNA-based therapies for neurodegenerative diseases.
Author: Suvi Asikainen
Institution: University of Eastern Finland
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: NordForsk, Saastamoisen säätiö
OpenAlex ID: W2143752913