Eucaryotic cells have two different sets of tRNAs which are encoded by nuclear and mitochondrial DNA.Both populations of tRNAs go through maturation process. One of the enzymes essential for this process is RNaseZ endonuclease. In mitochondria endonucleolytic activity of RNAseZ serves not only to edit tRNAs but also is essential for processing of mRNAs coding for subunits of mitochondrial respiratory chain.
Figure 1- RNaseZ and mitochondrial transcript processing. RNaseZ cuts at the 3’ end of each tRNA thus separating them from mRNAs and rRNAs
Figure 2- (a) qPCR analysis of mtDNA in WT and Z∆MTS wing discs, mtDNA values are normalized to nuclear DNA (b) citrate synthase activity, the marker for mitochondrial mass
Figure 3-Z∆MTS = mutant phenotype, WT = wild type. (a) RT-PCR results for the studied gene products. rp49 is a housekeeping gene. (b) Results of analysis of relative band intensity.
Figure 4-Model for the mechanism enabling the increase of mitochondrial mass and amount of DNA under condition of mitochondria failure. When mitochondrial function fails due to lack of RNaseZ, mitochondria sends signals to nucleus to upregulate tamas and mtSSB genes thus enabling production of more mitochondria
RNaseZ is a highly conserved gene, whose mutations were linked to prostate cancer and infantile hypertrophic cardiomyopathy in humans.To understand the role of this gene in such diseases the function of the protein encoded by this gene is studied using Drosophila flies as a model. When this protein is removed from mitochondria, the function of respiratory chain fails. In such cells the amount of mitochondria and mitochondrial DNA is drastically increased. The goal of this study is to identify the targets of retrograde signaling activating mitochondria biosynthesis.
I would like to give a sincere thanks to Dr. Rubin for his expert guidance through this project. I would also like to thank Catharina Grubaugh and Anthony Evans for their endless patience and all their time devoted to help us. I appreciate Dr. Dubrovsky’s lab for kindly providing the Drosophila stocks.
|This document was last modified 05/16/2016.|
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