Mitochondria are cellular organelles that are present in all nucleated eukaryotic cells and contain their own genome (mtDNA). Mitochondrial DNA encodes beside 13 polypeptides and 22 tRNAs, 2 ribosomal RNAs. All mtDNA encoded proteins are synthesized within the mitochondrial matrix and essential parts of intra membrane multi-enzyme complexes, involved in oxidative phosphorylation. Mitochondrial protein synthesis is therefore essential for life. This process, however, is still poorly understood. Around 100 mitoribosomal proteins, initiation and elongations factors are involved in mitochondrial translation but the exact mechanisms of how the mitochondrial 55S monosome and the constituted subunits assemble remain obscure. In an attempt to identify factors that play a role in mitoribosome assembly, proteomic analyses of affinity purified complexes using mtRRF were performed (Rorbach et al., 2008). One identified protein was ERAL1, a KH domain containing GTPase with sequence similarity to Era, a eubacterial protein involved in maturation of the 16SrRNA. SiRNA mediated ERAL1 depletion experiments in human cell lines were established and used to investigate the molecular function of the protein. As data in this thesis show, ERAL1 is a mitochondrial protein and is essential for mammalian cells. ERAL1 acts in mitochondria as a 12S-rRNA chaperone via binding at a conserved stem loop structure close to the 3’ terminus of the 12S-rRNA and loss affects the assembly of the small mitoribosomal subunit. Depletion of ERAL1 causes its major growth phenotype, partly by inducing apoptosis. Thus the mitochondrial oxidative phosphorylation machinery is not affected during ERAL1 depletion. ERAL1 is therefore an essential protein in eukaryotic cells, involved in 12S-rRNA maintenance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:556035 |
| Date | January 2011 |
| Creators | Dennerlein, Sven |
| Publisher | University of Newcastle Upon Tyne |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10443/1250 |
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