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Many nuclear genes encoding mitochondrial proteins require specific localization of their mRNAs to the vicinity of mitochondria for proper expression. Studies in Saccharomyces cerevisiae have shown that the cis-acting signal responsible for subcellular localization of mRNAs is localized in the 3' UTR of the transcript. In this paper we present an in silico approach for prediction of a common perimitochondrial localization signal of nuclear transcripts encoding mitochondrial proteins. We computed a consensus structure for this signal by comparison of 3' UTR models for about 3000 yeast transcripts with known localization. Our studies show a short stem-loop structure which appears in most mRNAs localized to the vicinity of mitochondria. The degree of similarity of a given 3' UTR to our consensus structure strongly correlates with experimentally determined perimitochondrial localization of the mRNA, therefore we believe that the structure we predicted acts as a subcellular localization signal. Since our algorithm operates on structures, it seems to be more reliable than sequence-based algorithms. The good predictive value of our model is supported by statistical analysis.
Many models of tumour formation have been put forth so far. In general they involve mutations in at least three elements within the cell: oncogenes, tumour suppressors and regulators of telomere replication. Recently numerous mutations in mitochondria have been found in many tumours, whereas they were absent in normal tissues from the same individual. The presence of mutations, of course, does not prove that they play a causative role in development of neoplastic lesions and progression; however, the key role played by mitochondria in both apoptosis and generation of DNA-damaging reactive oxygen species might indicate that the observed mutations contribute to tumour development. Recent experiments with nude mice have proven that mtDNA mutations are indeed responsible for tumour growth and exacerbated ROS production. This review describes mtDNA mutations in main types of human neoplasia.
We have cloned and sequenced a cDNA of the human homologue of the Saccharomyces cerevisiae Suv3 putative RNA helicase which is indispensable for mitochondrial function in yeast. The human Suv-3-like protein has a typical mitochondrial leader sequence. Northern blot data and analysis of ESTs in the data banks indicate that this human gene (SUPV3L1) is expressed in practically all tissues, though at different levels. Sequence homology analysis has shown a strong conservation of the protein in a number of eukaryotic organisms - plants, mammals and fungi, but no close homologues exist in bacteria with the exception of the purple bacterium Rhodobacter sphaeroides. This gene is thus ubiquitously present in all eukaryotic organisms.
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