Differential regulation of the duplicated isocytochrome c genes in yeast.

Abstract

The 2 unlinked genes CYC1 and CYC7 encode iso-1-cytochrome c and iso-2-cytochrome c, respectively, in the yeast S. cerevisiae. An examination of the steady-state level of CYC1 and CYC7 mRNA in normal and mutant strains grown under different conditions, along with previous results of apoprotein levels, demonstrate that CYC1 and CYC7 have similar and different modes of regulation. Both CYC1 and CYC7 mRNA are diminished after anaerobic growth. In contrast, CYC1 mRNA but not CYC7 mRNA is decreased by heme deficiency in hem1 mutants. Although both CYC1 and CYC7 mRNA are substantially lowered after growth in glucose medium, there is a difference in the kinetics of glucose derepression. CYC1 mRNA levels rise in the early logarithmic phase of growth before complete exhaustion of glucose, whereas CYC7 mRNA levels rise in the late logarithmic phase when the level of CYC1 mRNA plateaus. For a brief period before cessation of growth, the level of CYC7 mRNA attains a level corresponding to the high derepressed level of CYC1 mRNA. The high amount of CYC7 mRNA is surprising because iso-2-cytochrome c constitutes only 5% of the total cytochrome c complement in derepressed cells. Iso-2-cytochrome c has the potential to comprise a major proportion of cytochrome c under certain physiologic conditions that have not been experimentally defined. The cyc3 mutant, which lacks the ability to attach heme groups to apocytochromes c, contains both CYC1 and CYC7 mRNA in normal amounts. cyc3 mutants contain only apoiso-2-cytochrome c and not apoiso-1-cytochrome c. The lack of accumulation of apoiso-1-cytochrome c in ccy3 mutants, which contain CYC1 mRNA, suggests that apoiso-1-cytochrome c is extensively regulated by a post-transcriptional process.