FUNCTIONAL INTERACTIONS BETWEEN YEAST MITOCHONDRIAL RIBOSOMES AND MESSENGER-RNA 5'-UNTRANSLATED LEADERS

Translation of mitochondrial mRNAs in Saccharomyces cerevisiae depends on mRNA-specific translational activators that recognize the 5' untra nslated leaders (5'-UTLs) of their target mRNAs. We have identified mu tations in two new nuclear genes that suppress translation defects due to certain alterations in the 5'-UTLs of both the COX2 and COX3 mRNAs , indicating a general function in translational activation, lane gene , MRP21, encodes a protein with a domain related to the bacterial ribo somal protein S21 and to unidentified proteins of several animals, The other gene, MRP51, encodes a novel protein whose only known homolog i s encoded by an unidentified gene in S. kluyveri. Deletion of either M RP21 or MRP51 completely blocked mitochondrial gene expression. Submit ochondrial fractionation showed that both Mrp21p and Mrp51p cosediment with the mitochondrial ribosomal small subunit, That suppressor mutat ions are missense substitutions, and those affecting Mrp21p alter the region homologous to E. coli S21, which is known to interact with mRNA s. Interactions of the suppressor mutations with leaky mitochondrial i nitiation codon mutations strongly suggest that the suppressors do not generally increase translational efficiency, since some alleles that strongly suppress 5'-UTL mutations fail to suppress initiation codon m utations. We propose that mitochondrial ribosomes themselves recognize a common feature of mRNA 5'-UTLs which, in conjunction with mRNA-spec ific translational activation, is required for organellar translation initiation.