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A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development
The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filament...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495915/ https://www.ncbi.nlm.nih.gov/pubmed/23152891 http://dx.doi.org/10.1371/journal.pone.0049292 |
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author | Servos, Jörg Hamann, Andrea Grimm, Carolin Osiewacz, Heinz D. |
author_facet | Servos, Jörg Hamann, Andrea Grimm, Carolin Osiewacz, Heinz D. |
author_sort | Servos, Jörg |
collection | PubMed |
description | The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development. |
format | Online Article Text |
id | pubmed-3495915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34959152012-11-14 A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development Servos, Jörg Hamann, Andrea Grimm, Carolin Osiewacz, Heinz D. PLoS One Research Article The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development. Public Library of Science 2012-11-12 /pmc/articles/PMC3495915/ /pubmed/23152891 http://dx.doi.org/10.1371/journal.pone.0049292 Text en © 2012 Servos 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 Servos, Jörg Hamann, Andrea Grimm, Carolin Osiewacz, Heinz D. A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title | A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title_full | A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title_fullStr | A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title_full_unstemmed | A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title_short | A Differential Genome-Wide Transcriptome Analysis: Impact of Cellular Copper on Complex Biological Processes like Aging and Development |
title_sort | differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495915/ https://www.ncbi.nlm.nih.gov/pubmed/23152891 http://dx.doi.org/10.1371/journal.pone.0049292 |
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