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Connecting Variability in Global Transcription Rate to Mitochondrial Variability

das Neves, RP; Jones, NS; Andreu, L; Gupta, R; Enver, T; Iborra, FJ; (2010) Connecting Variability in Global Transcription Rate to Mitochondrial Variability. PLOS BIOL , 8 (12) , Article e1000560. 10.1371/journal.pbio.1000560. Green open access

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Abstract

Populations of genetically identical eukaryotic cells show significant cell-to-cell variability in gene expression. However, we lack a good understanding of the origins of this variation. We have found marked cell-to-cell variability in average cellular rates of transcription. We also found marked cell-to-cell variability in the amount of cellular mitochondrial mass. We undertook fusion studies that suggested that variability in transcription rate depends on small diffusible factors. Following this, in vitro studies showed that transcription rate has a sensitive dependence on [ATP] but not on the concentration of other nucleotide triphosphates (NTPs). Further experiments that perturbed populations by changing nutrient levels and available [ATP] suggested this connection holds in vivo. We found evidence that cells with higher mitochondrial mass, or higher total membrane potential, have a faster rate of transcription per unit volume of nuclear material. We also found evidence that transcription rate variability is substantially modulated by the presence of anti- or prooxidants. Daughter studies showed that a cause of variability in mitochondrial content is apparently stochastic segregation of mitochondria at division. We conclude by noting that daughters that stochastically inherit a lower mitochondrial mass than their sisters have relatively longer cell cycles. Our findings reveal a link between variability in energy metabolism and variability in transcription rate.

Type: Article
Title: Connecting Variability in Global Transcription Rate to Mitochondrial Variability
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pbio.1000560
Publisher version: http://dx.doi.org/10.1371/journal.pbio.1000560
Language: English
Additional information: © 2010 Pires das Neves et al. 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 credited. Funding: This work has been founded by the Ministerio de Ciencia e Innovacion (Spain) (BFU2009-10792) and the Medical Research Council (UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: RNA-POLYMERASE-II, STOCHASTIC GENE-EXPRESSION, CELLS, PROTEIN, NOISE, MODEL, CONSEQUENCES, KINETICS, NUCLEUS, ORIGINS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1336702
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