title: Regulation of mitochondrial translation of the ATP8/ATP6 mRNA by Smt1p.
abstract: Expression of the mitochondrially encoded ATP6 and ATP8 genes is translationally regulated by F1 ATPase. We report a translational repressor (Smt1p) of the ATP6/8 mRNA that, when mutated, restores translation of the encoded Atp6p and Atp8p subunits of the ATP synthase. Heterozygous smt1 mutants fail to rescue the translation defect, indicating that the mutations are recessive. Smt1p is an intrinsic inner membrane protein, which, based on its sedimentation, has a native size twice that of the monomer. Affinity purification of tagged Smt1p followed by reverse transcription of the associated RNA and PCR amplification of the resultant cDNA with gene-specific primers demonstrated the presence in mitochondria of Smt1p-ATP8/ATP6 and Smt1p-COB mRNA complexes. These results indicate that Smt1p is likely to be involved in translational regulation of both mRNAs. Applying Occam's principle, we favor a mechanistic model in which translation of the ATP8/ATP6 bicistronic mRNA is coupled to the availability of F1 for subsequent assembly of the Atp6p and Atp8p products into the ATP synthase. The mechanism of this regulatory pathway is proposed to entail a displacement of the repressor from the translationally mute Smt1-ATP8/ATP6 complex by F1, thereby permitting the Atp22p activator to interact with and promote translation of the mRNA.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rak
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Chen Hsien
authors.initials: CH
authors.lastname: Su
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Jonathan Tong
authors.initials: JT
authors.lastname: Xu
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azpiroz
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors.forename: Angela Mohan
authors.initials: AM
authors.lastname: Singh
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027 spud@columbia.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tzagoloff
mesh_terms: D015966:Gene Expression Regulation, Fungal; D008780:Methyltransferases / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D014176:Protein Biosynthesis; D006180:Proton-Translocating ATPases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: C501004:ATP6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008780:Methyltransferases; C000613397:SMT1 protein, S cerevisiae; C550189:ATP22 protein, S cerevisiae; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; C545198:Atp8 protein, S cerevisiae
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