Overexpression of the COX2 translational activator, Pet111p, prevents translation of COX1 mRNA and cytochrome c oxidase assembly in mitochondria of Saccharomyces cerevisiae.
Dramatically elevated levels of the COX2 mitochondrial mRNA-specific translational activator protein Pet111p interfere with respiratory growth and cytochrome c oxidase accumulation. The respiratory phenotype appears to be caused primarily by inhibition of the COX1 mitochondrial mRNA translation, a finding confirmed by lack of cox1Delta::ARG8(m) reporter mRNA translation. Interference with Cox1p synthesis depends to a limited extent upon increased translation of the COX2 mRNA, but is largely independent of it. Respiratory growth is partially restored by a chimeric COX1 mRNA bearing the untranslated regions of the COX2 mRNA, and by overproduction of the COX1 mRNA-specific activators, Pet309p and Mss51p. These results suggest that excess Pet111p interacts unproductively with factors required for normal COX1 mRNA translation. Certain missense mutations in PET111 alleviate the interference with COX1 mRNA translation but do not completely restore normal respiratory growth in strains overproducing Pet111p, suggesting that elevated Pet111p also perturbs assembly of newly synthesized subunits into active cytochrome c oxidase. Thus, this severe imbalance in translational activator levels appears to cause multiple problems in mitochondrial gene expression, reflecting the dual role of balanced translational activators in cooperatively regulating both the levels and locations of organellar translation.
Fiori
Alessandro
A
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.
Perez-Martinez
Xochitl
X
Fox
Thomas D
TD
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008565:Membrane Proteins; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010448:Peptide Initiation Factors; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C087048:PET111 protein, S cerevisiae; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D029701:Saccharomyces cerevisiae Proteins; C029305:mitochondrial messenger RNA; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003576:Electron Transport Complex IV