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Post-transcriptional regulation of human mitochondrial gene expression

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It is estimated that 3 – 5 % of all human proteins are localised to mitochondria, vital organelles that supply energy to the cell through the process of oxidative phosphorylation (OXPHOS). However, mitochondria are also involved in other important cellular processes such as Fe-S cluster biosynthesis, nucleotide biosynthesis, calcium homoeostasis, apoptosis or tumorigenesis. Approximately 90 proteins form the five enzyme complexes that perform OXPHOS and 13 of those are encoded in the mitochondrial genome – circular, multicopy (up to 1000 copies per cell), 16.5-kb molecule often referred as mtDNA. For this reason mitochondria contain a separate genetic system, necessary for the expression of the mtDNA-encoded polypeptides of the OXPHOS system. Transcription of both strands of mtDNA yields precursor polycistronic RNAs, from which the full panoply of mature mitochondrial transcripts is generated. Processed mitochondrial mRNAs are polyadenylated and in many instances the addition of the poly(A) tail is required to complete stop codon, however the exact function of human mitochondrial poly(A) tails is unclear. In addition to the mRNAs coding for the respiratory chain subunits, the mitochondrial genome also encodes 2 rRNAs and 22 tRNAs that are required for intra-mitochondrial protein synthesis by dedicated ribosomes (mitoribosomes). All protein components involved in mitochondrial gene expression including RNA polymerase, transcription factors, RNA processing enzymes, mitochondrial ribosomal subunits, translation factors et al. are encoded by nuclear genes and imported to mitochondria from the cytosol. Currently, we try to understand the regulation of mitochondrial gene expression. We focus on identifying and isolating new factors that are important for the post-transcriptional stages of mitochondrial gene expression. During my talk I will describe our recent work on proteins regulating mitochondrial RNA polyadenylation and mitoribosome biogenesis.

This talk is part of the Genetics Seminar Series series.

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