Stochastic mRNA Synthesis in Mammalian Cells
Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated...
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Public Library of Science
2006
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563489/ |
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pubmed-15634892006-09-12 Stochastic mRNA Synthesis in Mammalian Cells Raj, Arjun Peskin, Charles S Tranchina, Daniel Vargas, Diana Y Tyagi, Sanjay Research Article Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cell's genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the gene transitions from an inactive to an active state and ending when they transition back to the inactive state. We show that these transitions are intrinsically random and not due to global, extrinsic factors such as the levels of transcriptional activators. Moreover, the gene activation causes burst-like expression of all genes within a wider genomic locus. We further found that bursts are also exhibited in the synthesis of natural genes. The bursts of mRNA expression can be buffered at the protein level by slow protein degradation rates. A stochastic model of gene activation and inactivation was developed to explain the statistical properties of the bursts. The model showed that increasing the level of transcription factors increases the average size of the bursts rather than their frequency. These results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise. Public Library of Science 2006-10 2006-09-12 /pmc/articles/PMC1563489/ /pubmed/17048983 http://dx.doi.org/10.1371/journal.pbio.0040309 Text en © 2006 Raj 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Raj, Arjun Peskin, Charles S Tranchina, Daniel Vargas, Diana Y Tyagi, Sanjay |
| spellingShingle |
Raj, Arjun Peskin, Charles S Tranchina, Daniel Vargas, Diana Y Tyagi, Sanjay Stochastic mRNA Synthesis in Mammalian Cells |
| author_facet |
Raj, Arjun Peskin, Charles S Tranchina, Daniel Vargas, Diana Y Tyagi, Sanjay |
| author_sort |
Raj, Arjun |
| title |
Stochastic mRNA Synthesis in Mammalian Cells |
| title_short |
Stochastic mRNA Synthesis in Mammalian Cells |
| title_full |
Stochastic mRNA Synthesis in Mammalian Cells |
| title_fullStr |
Stochastic mRNA Synthesis in Mammalian Cells |
| title_full_unstemmed |
Stochastic mRNA Synthesis in Mammalian Cells |
| title_sort |
stochastic mrna synthesis in mammalian cells |
| description |
Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cell's genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the gene transitions from an inactive to an active state and ending when they transition back to the inactive state. We show that these transitions are intrinsically random and not due to global, extrinsic factors such as the levels of transcriptional activators. Moreover, the gene activation causes burst-like expression of all genes within a wider genomic locus. We further found that bursts are also exhibited in the synthesis of natural genes. The bursts of mRNA expression can be buffered at the protein level by slow protein degradation rates. A stochastic model of gene activation and inactivation was developed to explain the statistical properties of the bursts. The model showed that increasing the level of transcription factors increases the average size of the bursts rather than their frequency. These results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise.
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| publisher |
Public Library of Science |
| publishDate |
2006 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563489/ |
| _version_ |
1611387400295022592 |