An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing.
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.
Autio
Kaija J
KJ
Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O. Box 3000, FIN-90014 Oulu, Finland. kalervo.hiltunen@oulu.fi.
Kastaniotis
Alexander J
AJ
Pospiech
Helmut
H
Miinalainen
Ilkka J
IJ
Schonauer
Melissa S
MS
Dieckmann
Carol L
CL
Hiltunen
J Kalervo
JK
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D016678:Genome / Q000235:genetics; D006801:Humans; D006836:Hydro-Lyases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D012313:RNA / Q000235:genetics*; D043262:Ribonuclease P / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics; D014714:Vertebrates / Q000235:genetics* / Q000378:metabolism*
D018076:DNA, Complementary; D005227:Fatty Acids; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; C468368:RPP14 protein, human; D043262:Ribonuclease P; C495281:Htd2 protein, S cerevisiae; D006836:Hydro-Lyases