Stochastic mRNA synthesis in mammalian cells

Arjun Raj, Charles S. Peskin, Daniel Tranchina, Diana Y. Vargas, Sanjay Tyagi

Research output: Contribution to journalArticle

809 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1707-1719
Number of pages13
JournalPLoS biology
Volume4
Issue number10
DOIs
StatePublished - Oct 30 2006

Fingerprint

Genes
Cells
Messenger RNA
synthesis
gene activation
cells
Transcriptional Activation
Molecules
Gene Expression
Chemical activation
genes
Gene Silencing
Proteins
protein degradation
Reporter Genes
reporter genes
Proteolysis
Transcription
Stochastic models
Noise

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Raj, A., Peskin, C. S., Tranchina, D., Vargas, D. Y., & Tyagi, S. (2006). Stochastic mRNA synthesis in mammalian cells. PLoS biology, 4(10), 1707-1719. https://doi.org/10.1371/journal.pbio.0040309
Raj, Arjun ; Peskin, Charles S. ; Tranchina, Daniel ; Vargas, Diana Y. ; Tyagi, Sanjay. / Stochastic mRNA synthesis in mammalian cells. In: PLoS biology. 2006 ; Vol. 4, No. 10. pp. 1707-1719.
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Raj, A, Peskin, CS, Tranchina, D, Vargas, DY & Tyagi, S 2006, 'Stochastic mRNA synthesis in mammalian cells', PLoS biology, vol. 4, no. 10, pp. 1707-1719. https://doi.org/10.1371/journal.pbio.0040309

Stochastic mRNA synthesis in mammalian cells. / Raj, Arjun; Peskin, Charles S.; Tranchina, Daniel; Vargas, Diana Y.; Tyagi, Sanjay.

In: PLoS biology, Vol. 4, No. 10, 30.10.2006, p. 1707-1719.

Research output: Contribution to journalArticle

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Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S. Stochastic mRNA synthesis in mammalian cells. PLoS biology. 2006 Oct 30;4(10):1707-1719. https://doi.org/10.1371/journal.pbio.0040309