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The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity
Nutrient fluctuations in the cellular environment promote changes in cell metabolism and growth to adapt cell proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role in the coordination of growth and cell proliferation with the nutrient environment and, important...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990653/ https://www.ncbi.nlm.nih.gov/pubmed/29720420 http://dx.doi.org/10.1098/rsob.180015 |
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author | Lie, Shervi Banks, Peter Lawless, Conor Lydall, David Petersen, Janni |
author_facet | Lie, Shervi Banks, Peter Lawless, Conor Lydall, David Petersen, Janni |
author_sort | Lie, Shervi |
collection | PubMed |
description | Nutrient fluctuations in the cellular environment promote changes in cell metabolism and growth to adapt cell proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role in the coordination of growth and cell proliferation with the nutrient environment and, importantly, nutrient limitation reduces TOR complex 1 (TORC1) signalling. We have performed global quantitative fitness profiling of the collection of Schizosaccharomyces pombe strains from which non-essential genes have been deleted. We identified genes that regulate fitness when cells are grown in a nutrient-rich environment compared with minimal environments, with varying nitrogen sources including ammonium, glutamate and proline. In addition, we have performed the first global screen for genes that regulate fitness when both TORC1 and TORC2 signalling is reduced by Torin1. Analysis of genes whose deletions altered fitness when nutrients were limited, or when TOR signalling was compromised, identified a large number of genes that regulate transmembrane transport, transcription and chromatin organization/regulation and vesicle-mediated transport. The ability to tolerate reduced TOR signalling placed demands upon a large number of biological processes including autophagy, mRNA metabolic processing and nucleocytoplasmic transport. Importantly, novel biological processes and all processes known to be regulated by TOR were identified in our screens. In addition, deletion of 62 genes conserved in humans gave rise to strong sensitivity or resistance to Torin1, and 29 of these 62 genes have novel links to TOR signalling. The identification of chromatin and transcriptional regulation, nutritional uptake and transport pathways in this powerful genetic model now paves the way for a molecular understanding of how cells adapt to the chronic and acute fluctuations in nutrient supply that all eukaryotes experience at some stage, and which is a key feature of cancer cells within solid tumours. |
format | Online Article Text |
id | pubmed-5990653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59906532018-06-11 The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity Lie, Shervi Banks, Peter Lawless, Conor Lydall, David Petersen, Janni Open Biol Research Nutrient fluctuations in the cellular environment promote changes in cell metabolism and growth to adapt cell proliferation accordingly. The target of rapamycin (TOR) signalling network plays a key role in the coordination of growth and cell proliferation with the nutrient environment and, importantly, nutrient limitation reduces TOR complex 1 (TORC1) signalling. We have performed global quantitative fitness profiling of the collection of Schizosaccharomyces pombe strains from which non-essential genes have been deleted. We identified genes that regulate fitness when cells are grown in a nutrient-rich environment compared with minimal environments, with varying nitrogen sources including ammonium, glutamate and proline. In addition, we have performed the first global screen for genes that regulate fitness when both TORC1 and TORC2 signalling is reduced by Torin1. Analysis of genes whose deletions altered fitness when nutrients were limited, or when TOR signalling was compromised, identified a large number of genes that regulate transmembrane transport, transcription and chromatin organization/regulation and vesicle-mediated transport. The ability to tolerate reduced TOR signalling placed demands upon a large number of biological processes including autophagy, mRNA metabolic processing and nucleocytoplasmic transport. Importantly, novel biological processes and all processes known to be regulated by TOR were identified in our screens. In addition, deletion of 62 genes conserved in humans gave rise to strong sensitivity or resistance to Torin1, and 29 of these 62 genes have novel links to TOR signalling. The identification of chromatin and transcriptional regulation, nutritional uptake and transport pathways in this powerful genetic model now paves the way for a molecular understanding of how cells adapt to the chronic and acute fluctuations in nutrient supply that all eukaryotes experience at some stage, and which is a key feature of cancer cells within solid tumours. The Royal Society 2018-05-02 /pmc/articles/PMC5990653/ /pubmed/29720420 http://dx.doi.org/10.1098/rsob.180015 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Lie, Shervi Banks, Peter Lawless, Conor Lydall, David Petersen, Janni The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title | The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title_full | The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title_fullStr | The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title_full_unstemmed | The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title_short | The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
title_sort | contribution of non-essential schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990653/ https://www.ncbi.nlm.nih.gov/pubmed/29720420 http://dx.doi.org/10.1098/rsob.180015 |
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