Interaction between the yeast mitochondrial and nuclear genomes influences the abundance of novel transcripts derived from the spacer region of the nuclear ribosomal DNA repeat.

Abstract

We have identified stable transcripts from the so-called nontranscribed spacer region (NTS) of the nuclear ribosomal DNA repeat in certain respiration-deficient strains of Saccharomyces cerevisiae. These RNAs, which are transcribed from the same strand as is the 37S rRNA precursor, are 500 to 800 nucleotides long and extend from the 5' end of the 5S rRNA gene to three major termination sites about 1,780, 1,830, and 1,870 nucleotides from the 3' end of the 26S rRNA gene. A survey of various wild-type and respiration-deficient strains showed that NTS transcript abundance depended on the mitochondrial genotype and a single codominant nuclear locus. In strains with that nuclear determinant, NTS transcripts were barely detected in [rho'] cells, were slightly more abundant in various mit-derivatives, and were most abundant in petites. However, in one petite that was hypersuppressive and contained a putative origin of replication (ori5) within its 757-base-pair mitochondrial genome, NTS transcripts were no more abundant than in [rho'] cells. The property of low NTS transcript abundance in the hypersuppressive petite was unstable, and spontaneous segregants that contained NTS transcripts as abundant as in the other petites examined could be obtained. Thus, respiration deficiency per se is not the major factor contributing to the accumulation of these unusual RNAs. Unlike RNA polymerase I transcripts, the abundant NTS RNAs were glucose repressible, fractionated as poly(A)+ RNAs, and were sensitive to inhibition by 10 ,ug of a-amanitin per ml, a concentration that had no effect on rRNA synthesis. Abundant NTS RNAs are therefore most likely derived by polymerase H transcription.Although the products of many nuclear genes and a few encoded by the mitochondrial genome are required for the synthesis of functional mitochondria, the molecular interactions between these organelles, which are required to achieve balanced mitochondrial synthesis, are still poorly understood. Expression of some nuclear genes encoding mitochondrial proteins is known to be regulated according to growth conditions and to various metabolic demands of the cell. In the yeast Saccharomyces cerevisiae, for example, growth of cells on high glucose concentrations represses the synthesis of nuclear-encoded components of the oxidative phosphorylation apparatus (55,62). Yeast cells also have a regulatory network that adjusts the synthesis of mitochondrial heme proteins in response to fluctuations in the levels of heme (21). These regulatory pathways operate through interactions between trans-acting factors encoded at loci such as HAP], HAP2, and HAP3 and their target, cis-acting sites located upstream of the relevant genes (22, 44 46, 58).Other nuclear genes have been identified which control mitochondrial gene expression in that their products exert specific control over mitochondrial RNA processing (3,13,14), mRNA stability (13-15), and translation (11,47,52 that the functional state of mitochondria, or the mitochondrial genotype, could influence the expre...

The Cytoplasm Affects the Epigenome in Drosophila melanogaster

“…Considering these heritable interaction effects on the phenotype is important because they can be as strong as the effects by the individual cytoplasmic components [8]. 2 of 11 Mitochondrial genomes have been widely reported to interact with nuclear genomes to affect phenotypic expression [6][7][8][9][10][11][12][13][14][15][16][17]. Nuclear and mitochondrial genomes also routinely coevolve within populations as suggested from studies reporting hybrid disadvantages observed when coadapted combinations of mito-nuclear genotypes have been experimentally disrupted by placing the mt genotype of one population alongside the nuclear genome of another population [13,[18][19][20].…”

“…Mitochondrial function is largely dependent on the nuclear genome, first and foremost due to the fact that the vast majority of proteins present in mitochondria are nuclear-encoded. However, studies have also shown or suggested that mitochondria can influence nuclear gene expression and might be involved in the epigenetic regulation of the nuclear genome [9,12,17,[28][29][30][31][32]. For instance, depleting mitochondria in cultured human kidney cells caused changes in nuclear DNA methylation, an important bearer of epigenetic information [33].…”

“…For instance, depleting mitochondria in cultured human kidney cells caused changes in nuclear DNA methylation, an important bearer of epigenetic information [33]. It is therefore conceivable that different mito-nuclear combinations might be under different epigenetic regulations and might entail the reported changes in life-history traits or disease [10,16,17,22,34]. Negative effects could arise from mito-nuclear mismatch (i.e., if a mitochondrial genotype is placed alongside a nuclear genomic background to which it has no close coevolutionary history and hence lacks the evolutionary 'optimization').…”

RTG-dependent Mitochondria-to-Nucleus Signaling Is Regulated by MKS1 and Is Linked to Formation of Yeast Prion [URE3]

“…Yeast cells also respond to mitochondrial dysfunction by altering the expression of a subset of nuclear genes (Parikh et al, 1987(Parikh et al, , 1989. This response, called retrograde regulation, functions to better adapt cells to the mitochondrial defects.…”

“…In animal cells, for example, compromises in mitochondrial function or certain external cues can lead to increased expression of genes encoding components of the mitochondrial oxidative phosphorylation apparatus and, in some instances, lead to a general increase in the biogenesis of mitochondria (Lunardi and Attardi, 1991;Scarpulla, 1997;Biswas et al, 1999;Heddi et al, 1999;Murdock et al, 1999;Wu et al, 1999;Amuthan et al, 2001). These events are controlled, in part, by transcriptional activators and coactivators whose targets include nuclear genes encoding mitochondrial proteins.Yeast cells also respond to mitochondrial dysfunction by altering the expression of a subset of nuclear genes (Parikh et al, 1987(Parikh et al, , 1989. This response, called retrograde regulation, functions to better adapt cells to the mitochondrial defects.…”