University of Natural Resources and Life Sciences, Vienna (BOKU) - Research portal
Gewählte Master / Diploma Thesis:
Elena Maria Stelzer
(2018):
The two ribosomal RNA methyltransferases NSUN5 and RRP8 modulate aging.
Master / Diploma Thesis - Institut für Biotechnologie,
BOKU-Universität für Bodenkultur,
pp 83.
UB BOKU
obvsg
- Abstract:
- Aging is a topic that gathers more attention within our modern society since the overall life expectancy is continuously rising. It is a process that involves a progressive loss of physiological integrity, an increase in age-related weakness and impairment, inevitably leading to death. Researchers try to better understand molecular processes, genetic and environmental parameters to extend the period of life we can spend without suffering from chronic diseases and disability. The present work is structured in two main parts investigating the two ribosomal RNA methyltransferases NSUN5 and RRP8 and their connection with aging. rRNA modifications seem to be essential for proper ribosome functionality and correct interaction of ribosome and mRNA template. A knockout of NSUN5 was already proofed to increase lifespan and stress resistance in several model organisms, such as yeast, flies and worms. Within the present thesis, a successful knockout of NSUN5 in the two models Mus musculus and immortalized HeLa human cell line was confirmed. During an attempt to restore the methylation activity of NSUN5 in the human cell model, the control cells showed as well a high loss of methylation activity. This cellular stress was found to be a supposed downregulator of the methyltransferase. A possible influence of rRNA methylation due to aging or differences in the nutrient supply was investigated using C. elegans as a model organism. Here, no change was detected. On the one hand, RRP8 acts as a methyltransferase and, on the other hand, it plays an essential role in assembling the energy-dependent nucleolar silencing complex (eNoSC). With increasing age, C. elegans showed a slight increase in RRP-8 methylation activity and mRNA level. Dietary restriction which is known to be associated with prolonged lifespan led to a decrease in methylation. A knockout of this enzyme in C. elegans has already shown to extend the lifespan and delay aging, which correlates with the results found here.
- Beurteilende(r): Grillari Johannes
- 1.Mitwirkender: Schosserer Markus