Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.5 (RNase P)
 1,348 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In bacteria, functionally related gene products are often encoded by a common transcript. Such polycistronic transcripts are rare in eukaryotes. Here we isolated several clones from human cDNA libraries, which rescued the respiratory-deficient phenotype of a yeast mitochondrial 3-hydroxyacyl thioester dehydratase 2 (htd2) mutant strain. All complementing cDNAs were derived from the RPP14 transcript previously described to encode the RPP14 subunit of the human ribonuclease P (RNase P) complex. We identified a second, 3' open reading frame (ORF) on the RPP14 transcript encoding a protein showing similarity to known dehydratases and hydratase 2 enzymes. The protein was localized in mitochondria, and the recombinant enzyme exhibited (3R)-specific hydratase 2 activity. Based on our results, we named the protein human 3-hydroxyacyl-thioester dehydratase 2 (HsHTD2), which is involved in mitochondrial fatty acid synthesis. The bicistronic arrangement of RPP14 and HsHTD2, as well as the general exon structure of the gene, is conserved in vertebrates from fish to humans, indicating a genetic link conserved for 400 million years between RNA processing and mitochondrial fatty acid synthesis.
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PMID:An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing. 1789 86

Eukaryotes harbor a highly conserved mitochondrial pathway for fatty acid synthesis (FAS), which is completely independent of the eukaryotic cytosolic FAS apparatus. The activities of the mitochondrial FAS system are catalyzed by soluble enzymes, and the pathway thus resembles its prokaryotic counterparts. Except for octanoic acid, which is the direct precursor for lipoic acid synthesis, other end products and functions of the mitochondrial FAS pathway are still largely enigmatic. In addition to low cellular levels of lipoic acid, disruption of genes encoding mitochondrial FAS enzymes in yeast results in a respiratory-deficient phenotype and small rudimentary mitochondria. Recently, two distinct links between mitochondrial FAS and RNA processing have been discovered in vertebrates and yeast, respectively. In vertebrates, the mitochondrial 3-hydroxyacyl-acyl carrier protein dehydratase and the RPP14 subunit of RNase P are encoded by the same bicistronic transcript in an evolutionarily conserved arrangement that is unusual for eukaryotes. In yeast, defects in mitochondrial FAS result in inefficient RNase P cleavage in the organelle. The intersection of mitochondrial FAS and RNA metabolism in both systems provides a novel mechanism for the coordination of intermediary metabolism in eukaryotic cells.
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PMID:Mitochondrial fatty acid synthesis type II: more than just fatty acids. 1902 88

The highly conserved fatty acid de novo synthesis pathway in mitochondria proceeds in an acyl carrier protein-dependent manner through a discrete set of enzymes. Saccharomyces cerevisiae has served as a model for studies of mitochondrial fatty acid synthesis type II (FAS II) and as a template for identification of mammalian components. Inactivation of mitochondrial FAS II in yeast results in respiratory deficiency and loss of cytochromes. The pathway produces the octanoyl-ACP substrate for lipoic acid synthesis, but several pieces of evidence indicate that it is capable of the generation of longer fatty acids. A number of structures of mitochondrial FAS II enzymes have been published in the past few years, allowing for a comparison with their prokaryotic counterparts, several of which have been described as promising targets for antibiotics. Recently, novel links between mitochondrial FAS and RNA processing in yeast and vertebrates have been reported. In S. cerevisiae, deficiency in mitochondrial FAS results in failure of maturation of mitochondrial RNAse P, while, in mammals, mitochondrial 3-hydroxyacyl thioester dehydratase and the RPP14 subunit of RNase P are encoded by the same bicistronic transcript. The first publications linking mitochondrial FAS II to disease states in mammals are emerging.
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PMID:Mitochondrial fatty acid synthesis--an adopted set of enzymes making a pathway of major importance for the cellular metabolism. 1968 77