Expression and evolution of the non-canonically translated yeast mitochondrial acetyl-CoA carboxylase Hfa1p.

TitleExpression and evolution of the non-canonically translated yeast mitochondrial acetyl-CoA carboxylase Hfa1p.
Publication TypeJournal Article
Year of Publication2014
AuthorsSuomi, F, Menger, KE, Monteuuis, G, Naumann, U, Kursu, VASamuli, Shvetsova, A, Kastaniotis, AJ
JournalPLoS One
Volume9
Issue12
Paginatione114738
Date Published2014
ISSN1932-6203
Keywords5' Untranslated Regions, Acetyl-CoA Carboxylase, Base Sequence, Codon, Initiator, Evolution, Molecular, Gene Expression Regulation, Fungal, Kluyveromyces, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Mutation, Peptide Chain Initiation, Translational, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription, Genetic
Abstract

The Saccharomyces cerevisiae genome encodes two sequence related acetyl-CoA carboxylases, the cytosolic Acc1p and the mitochondrial Hfa1p, required for respiratory function. Several aspects of expression of the HFA1 gene and its evolutionary origin have remained unclear. Here, we determined the HFA1 transcription initiation sites by 5' RACE analysis. Using a novel "Stop codon scanning" approach, we mapped the location of the HFA1 translation initiation site to an upstream AUU codon at position -372 relative to the annotated start codon. This upstream initiation leads to production of a mitochondrial targeting sequence preceding the ACC domains of the protein. In silico analyses of fungal ACC genes revealed conserved "cryptic" upstream mitochondrial targeting sequences in yeast species that have not undergone a whole genome duplication. Our Δhfa1 baker's yeast mutant phenotype rescue studies using the protoploid Kluyveromyces lactis ACC confirmed functionality of the cryptic upstream mitochondrial targeting signal. These results lend strong experimental support to the hypothesis that the mitochondrial and cytosolic acetyl-CoA carboxylases in S. cerevisiae have evolved from a single gene encoding both the mitochondrial and cytosolic isoforms. Leaning on a cursory survey of a group of genes of our interest, we propose that cryptic 5' upstream mitochondrial targeting sequences may be more abundant in eukaryotes than anticipated thus far.

DOI10.1371/journal.pone.0114738
Alternate JournalPLoS ONE
Citation Key10.1371/journal.pone.0114738
PubMed ID25503745
PubMed Central IDPMC4263661