The functions of ICT1 and mtRbfA in the human mitochondrial ribosome

• Main Author: Richter, Ricarda
• Published: University of Newcastle upon Tyne 2011
• Subjects: 572.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542314

During the last decades our knowledge about the human mitochondrial translation system has been expanded. However, our understanding of this unique system is far from complete. Mitochondria contain a minimal genome, whose expression is dependent on factors encoded by the nuclear genome. Derived from a bacterial ancestor it is very close to the translation system found in bacteria, but there are also a lot of differences especially the translating ribosome, which differs in a number of features including the sedimentation coefficient, protein-RNA ratio and number of tRNA sites. Available cryo-EM structures of the mitochondrial ribosome are limited, making it difficult to understand the system completely. There are still a lot of open questions concerning the composition, assembly, translation initiation or the recycling of stalled ribosomes in mammalian mitochondria. The study presented in this thesis contributes to our understanding of this unique system by the characterisation of two mitochondrial proteins, found in association with the mitochondrial ribosome, ICT1 and mtRbfA. These proteins are found in association with the mitochondrial ribosome, and were immunoprecipitated together with the mitochondrial ribosome recycling factor (mtRRF). ICT1 as a member of the mitochondrial release factor family has been identified as a peptidyl-tRNA hydrolase. Data shown here indicates that ICT1 has been recruited into the mitochondrial ribosome and further, suggests the involvement of ICT1 in the rescue of stalled ribosomal complexes with immobilised peptidyl-tRNA. In contrast mtRbfA was identified as a potential ribosome assembly factor rather than a permanent component. The function of this protein is still elusive, but data generated for this thesis shows that this protein is preferentially associated with the mitochondrial ribosomal small subunit at a late assembly point, suggesting possible roles of mtRbfA in quality control or in translation initiation.