Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability
| Autor: | Hansen, Maike MK, Desai, Ravi V, Simpson, Michael L, Weinberger, Leor S |
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| Rok vydání: | 2018 |
| Předmět: |
Transcriptional Activation
Cytoplasm RNA Processing 1.1 Normal biological development and functioning Messenger Population Post-Transcriptional translation Jurkat Cells Mice Theoretical Models Underpinning research Genetics Animals Humans noise amplification Embryonic Stem Cells stochastic noise noise attenuation Human Genome mathematical modeling Biological Variation Single Molecule Imaging HEK293 Cells mRNA degradation RNA nuclear export Generic health relevance Biochemistry and Cell Biology Single-Cell Analysis bursting transcription single molecule RNA FISH |
| Zdroj: | Cell systems, vol 7, iss 4 |
| Popis: | Transcription is an episodic process characterized by probabilistic bursts, but how the transcriptional noise from these bursts is modulated by cellular physiology remains unclear. Using simulations and single-molecule RNA counting, we examined how cellular processes influence cell-to-cell variability (noise). The results show that RNA noise is higher in the cytoplasm than the nucleus in ∼85% of genes across diverse promoters, genomic loci, and cell types (human and mouse). Measurements show further amplification of RNA noise in the cytoplasm, fitting a model of biphasic mRNA conversion between translation- and degradation-competent states. This multi-state translation-degradation of mRNA also causes substantial noise amplification in protein levels, ultimately accounting for ∼74% of intrinsic protein variability in cell populations. Overall, the results demonstrate how noise from transcriptional bursts is intrinsically amplified by mRNA processing, leading to a large super-Poissonian variability in protein levels. |
| Databáze: | OpenAIRE |
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