RESUMO
Nuclear and mitochondrial organelles must maintain a communication system. Loci on the mitochondrial genome were recently reported to interact with nuclear loci. To determine whether this is part of a DNA based communication system we used genome conformation capture to map the global network of DNA-DNA interactions between the mitochondrial and nuclear genomes (Mito-nDNA) in Saccharomyces cerevisiae cells grown under three different metabolic conditions. The interactions that form between mitochondrial and nuclear loci are dependent on the metabolic state of the yeast. Moreover, the frequency of specific mitochondrial-nuclear interactions (i.e. COX1-MSY1 and Q0182-RSM7) showed significant reductions in the absence of mitochondrial encoded reverse transcriptase machinery. Furthermore, these reductions correlated with increases in the transcript levels of the nuclear loci (MSY1 and RSM7). We propose that these interactions represent an inter-organelle DNA mediated communication system and that reverse transcription of mitochondrial RNA plays a role in this process.
Assuntos
Núcleo Celular/genética , DNA Mitocondrial/genética , Organelas/metabolismo , Organelas/fisiologia , RNA Mensageiro/genética , Transcrição Gênica , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Transporte Biológico/fisiologia , Núcleo Celular/efeitos dos fármacos , Cromossomos Fúngicos/efeitos dos fármacos , Cromossomos Fúngicos/genética , Cromossomos Fúngicos/metabolismo , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , DNA Mitocondrial/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Epistasia Genética/efeitos dos fármacos , Epistasia Genética/fisiologia , Galactose/farmacologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Loci Gênicos/fisiologia , Glucose/farmacologia , Organelas/efeitos dos fármacos , Organelas/genética , RNA Fúngico/efeitos dos fármacos , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/ultraestrutura , Fatores de Tempo , Transcrição Gênica/efeitos dos fármacosRESUMO
The three-dimensional organization of genomes is dynamic and plays a critical role in the regulation of cellular development and phenotypes. Here we use proximity-based ligation methods (i.e. chromosome conformation capture [3C] and circularized chromosome confrmation capture [4C]) to explore the spatial organization of tRNA genes and their locus-specific interactions with the ribosomal DNA. Directed replacement of one lysine and two leucine tRNA loci shows that tRNA spatial organization depends on both tRNA coding sequence identity and the surrounding chromosomal loci. These observations support a model whereby the three-dimensional, spatial organization of tRNA loci within the nucleus utilizes tRNA gene-specific signals to affect local interactions, though broader organization of chromosomal regions are determined by factors outside the tRNA genes themselves.