Highly diverged homolog of Saccharomyces cerevisiae mitochondrial mRNA-specific translational activators have orthologous functions in other budding yeasts

Translation of mitochondrially coded mRNAs in Saccharomyces cerevisiae depe nds on membrane-bound mRNA-specific activator proteins, whose targets lie i n the mRNX 5'-untranslated leaders (5'-UTLs). In at least some cases, the a ctivators function to localize translation of hydrophobic proteins on the i nner membrane and are rate limiting for gene expression. We searched unsucc essfully in divergent budding easts for orthologs of the COX2- and COX3-spe cific translational activator genes, PET111, PET54, PET122, and PET494, by direct complementation. However, by screening for complementation of mutati ons in genes adjacent to the PET genes in S, cerevisiae, we obtained chromo somal segments containing highly diverged homologs of PET111 and PET122 fro m Saccharomyces kluyveri and of PET111 from Kluyveromyces lactis. All three of these genes failed to function in S. cerevisiae. We also found that the 5'-UTLs of the COX2 and COX3 mRNAs of S. kluyveri and K. lactis have littl e similarity to each other or to those of S. cerevisiae. To determine wheth er the PET111 and PET122 homologs carry out orthologous functions, we delet ed them from the S. kluyveri genome and deleted PET111 from die K. lactis g enome. The pet111 mutations in both species prevented COX2 translation, and the S. kluyveri pet122 mutation prevented COX3 translation. Thus, while th e sequences of these translational activator proteins and their 5'-UTL targ ets are highly diverged, their mRNA-specific functions are orthologous.