Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability

Cell Syst. 2018 Oct 24;7(4):384-397.e6. doi: 10.1016/j.cels.2018.08.002. Epub 2018 Sep 19.


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.

Keywords: bursting; mRNA degradation; mathematical modeling; noise amplification; noise attenuation; nuclear export; single molecule RNA FISH; stochastic noise; transcription; translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Variation, Population*
  • Cytoplasm / metabolism
  • Embryonic Stem Cells / metabolism
  • HEK293 Cells
  • Humans
  • Jurkat Cells
  • Mice
  • Models, Theoretical*
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Single Molecule Imaging
  • Single-Cell Analysis
  • Transcriptional Activation


  • RNA, Messenger