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

PLoS One

Sarah Dadon¹  Yael Garbian¹  Dan Mishmar¹  Ofer Ovadia² 

[1] Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;National Institute of Biotechnology (NIBN), Ben-Gurion University of the Negev, Beer-Sheva, Israel

关键词: Mitochondrial DNA;    Polymerase chain reaction;    Post-transcriptional gene regulation;    Kidneys;    DNA transcription;    Eukaryota;    Genome complexity;    Transcriptional control;   

DOI  :  10.1371/journal.pone.0009985

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY