Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability.
Cell Syst
; 7(4): 384-397.e6, 2018 10 24.
Article
in En
| MEDLINE
| ID: mdl-30243562
ABSTRACT
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 â¼85% 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 â¼74% 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
RNA Processing, Post-Transcriptional
/
Biological Variation, Population
/
Models, Theoretical
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Syst
Year:
2018
Document type:
Article