The long term objective of the proposed research is to understand the interactions between mitochondria and the nucleus that insure the balanced synthesis of functional mitochondria during cell growth and development. The present proposal deals with two regulatory paths in yeast, one from the nucleus to mitochondria, and the other from mitochondria back to the nucleus. In the former, we will investigate the function of a highly conserved dodecamer sequence, 5'-AAUAAUAUUCUU-3', found at the 3' end of all mitochondrial mRNAs, and identify proteins that interact with that sequence. In the proposed studies we will take advantage of our ability to transform mitochondria of living yeast cells with exogenous DNA. In related studies, we have found that the nuclear gene, suv3, is likely to play a central role in mitochondrial gene expression, affecting mRNA formation, RNA processing and stability, splicing and translation. Our immediate objectives are to characterize that gene and its allele, SUV3-1, to identify and characterize the suv3 gene product and determine how that product functions in mitochondrial gene expression. We will extend our studies on novel regulatory interactions we recently discovered in which the state of mitochondria and the mitochondrial genome affect expression of nuclear genes. As a model system, we will focus on unusual polymerase Il-derived transcripts from the so-called non-transcribed spacer region of the nuclear rDNA repeat. The steady-state abundance of these transcripts is profoundly affected by the mitochondrial genotype. We will assess the possible significance of these observations to unique control of rRNA synthesis related to the functional state of mitochondria. Finally, we will identify and characterize the relevant cis and trans control elements in selected nuclear genes responsible for determining their regulated expression by the functional state of mitochondria. These studies should contribute to a better understanding of how cells are able to regulate the synthesis of a complex organelle whose constituents are derived from two separate genomes.
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