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Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters

After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I), was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were...

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Autores principales: Garbian, Yael, Ovadia, Ofer, Dadon, Sarah, Mishmar, Dan
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848612/
https://www.ncbi.nlm.nih.gov/pubmed/20376309
http://dx.doi.org/10.1371/journal.pone.0009985
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author Garbian, Yael
Ovadia, Ofer
Dadon, Sarah
Mishmar, Dan
author_facet Garbian, Yael
Ovadia, Ofer
Dadon, Sarah
Mishmar, Dan
author_sort Garbian, Yael
collection PubMed
description After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I), was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were retained in the genome of the mitochondrion, the ancient symbiote of eukaryotes. This division, in combination with the three-fold increase in subunit number from bacteria (N = ∼14) to man (N = 45), renders the transcription regulation of OXPHOS complex I a challenge. Recently bioinformatics analysis of the promoter regions of all OXPHOS genes in mammals supported patterns of co-regulation, suggesting that natural selection favored a mechanism facilitating the transcriptional regulatory control of genes encoding subunits of these large protein complexes. Here, using real time PCR of mitochondrial (mtDNA)- and nuclear DNA (nDNA)-encoded transcripts in a panel of 13 different human tissues, we show that the expression pattern of OXPHOS complex I genes is regulated in several clusters. Firstly, all mtDNA-encoded complex I subunits (N = 7) share a similar expression pattern, distinct from all tested nDNA-encoded subunits (N = 10). Secondly, two sub-clusters of nDNA-encoded transcripts with significantly different expression patterns were observed. Thirdly, the expression patterns of two nDNA-encoded genes, NDUFA4 and NDUFA5, notably diverged from the rest of the nDNA-encoded subunits, suggesting a certain degree of tissue specificity. Finally, the expression pattern of the mtDNA-encoded ND4L gene diverged from the rest of the tested mtDNA-encoded transcripts that are regulated by the same promoter, consistent with post-transcriptional regulation. These findings suggest, for the first time, that the regulation of complex I subunits expression in humans is complex rather than reflecting global co-regulation.
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spelling pubmed-28486122010-04-07 Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters Garbian, Yael Ovadia, Ofer Dadon, Sarah Mishmar, Dan PLoS One Research Article After the radiation of eukaryotes, the NUO operon, controlling the transcription of the NADH dehydrogenase complex of the oxidative phosphorylation system (OXPHOS complex I), was broken down and genes encoding this protein complex were dispersed across the nuclear genome. Seven genes, however, were retained in the genome of the mitochondrion, the ancient symbiote of eukaryotes. This division, in combination with the three-fold increase in subunit number from bacteria (N = ∼14) to man (N = 45), renders the transcription regulation of OXPHOS complex I a challenge. Recently bioinformatics analysis of the promoter regions of all OXPHOS genes in mammals supported patterns of co-regulation, suggesting that natural selection favored a mechanism facilitating the transcriptional regulatory control of genes encoding subunits of these large protein complexes. Here, using real time PCR of mitochondrial (mtDNA)- and nuclear DNA (nDNA)-encoded transcripts in a panel of 13 different human tissues, we show that the expression pattern of OXPHOS complex I genes is regulated in several clusters. Firstly, all mtDNA-encoded complex I subunits (N = 7) share a similar expression pattern, distinct from all tested nDNA-encoded subunits (N = 10). Secondly, two sub-clusters of nDNA-encoded transcripts with significantly different expression patterns were observed. Thirdly, the expression patterns of two nDNA-encoded genes, NDUFA4 and NDUFA5, notably diverged from the rest of the nDNA-encoded subunits, suggesting a certain degree of tissue specificity. Finally, the expression pattern of the mtDNA-encoded ND4L gene diverged from the rest of the tested mtDNA-encoded transcripts that are regulated by the same promoter, consistent with post-transcriptional regulation. These findings suggest, for the first time, that the regulation of complex I subunits expression in humans is complex rather than reflecting global co-regulation. Public Library of Science 2010-04-01 /pmc/articles/PMC2848612/ /pubmed/20376309 http://dx.doi.org/10.1371/journal.pone.0009985 Text en Garbian et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Garbian, Yael
Ovadia, Ofer
Dadon, Sarah
Mishmar, Dan
Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title_full Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title_fullStr Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title_full_unstemmed Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title_short Gene Expression Patterns of Oxidative Phosphorylation Complex I Subunits Are Organized in Clusters
title_sort gene expression patterns of oxidative phosphorylation complex i subunits are organized in clusters
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848612/
https://www.ncbi.nlm.nih.gov/pubmed/20376309
http://dx.doi.org/10.1371/journal.pone.0009985
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