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An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing

Kaija J. Autio^*,,1, Alexander J. Kastaniotis^*,,1, Helmut Pospiech^*, Ilkka J. Miinalainen^*,, Melissa S. Schonauer, Carol L. Dieckmann and J. Kalervo Hiltunen^*,,2

^* Department of Biochemistry and

Biocenter Oulu, University of Oulu, Oulu, Finland; and

Department of Biochemistry and Molecular Biophysics and Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA

²Correspondence: Department of Biochemistry and Biocenter Oulu, University of Oulu, P.O. Box 3000, FIN-90014 Oulu, Finland. E-mail: kalervo.hiltunen{at}oulu.fi

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, K. J., Kastaniotis, A. J., Pospiech, H., Miinalainen, I. J., Schonauer, M. S., Dieckmann, C. L., Hiltunen, J. K. An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing.

Key Words: HsHTD2 • RNase P