Rpm2, the protein subunit of mitochondrial RNase P in Saccharomyces cerevisiae, also has a role in the translation of mitochondrially encoded subunits of cytochrome c oxidase

RPM2 is a Saccharomyces cerevisiae nuclear gene that encodes the protein su bunit of mitochondrial RNase P and has an unknown function essential for fe rmentative growth. Cells lacking mitochondrial RNase P cannot respire and a ccumulate lesions in their mitochondrial DNA. The effects of a new RPM2 all ele, rpm2-100, reveal a novel function of RPM2 in mitochondrial biogenesis. Cells with rpm2-100 as their only source of Rpm2p have correctly processed mitochondrial tRNAs but are still respiratory deficient. Mitochondrial mRN A and rRNA levels are reduced in rpm2-100 cells compared to wild type. The general reduction in mRNA is not reflected in a similar reduction in mitoch ondrial protein synthesis. Incorporation of labeled precursors into mitocho ndrially encoded Atp6, Atp8, Atp9, and Cytb protein was enhanced in the mut ant relative to wild type, while incorporation into Cox1p, Cox2p, Cox3p, an d Var1p was reduced. Pulse-chase analysis of mitochondrial translation reve aled decreased rates of translation of COX1, COX2, and COX3 mRNAs. This dec rease leads to low steady-state levels of Cox1p, Cox2p, and Cox3p, loss of visible spectra of aa(3) cytochromes, and low cytochrome c oxidase activity in mutant mitochondria. Thus, RPM2 has a previously unrecognized role in m itochondrial biogenesis, in addition to its role as a subunit of mitochondr ial RNase P. Moreover, there is a synthetic lethal interaction between the disruption of this novel respiratory function and the loss of wild-type mtD NA. This synthetic interaction explains why a complete deletion of RPM2 is lethal.