Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels
Year: 2016
Type: article
Abstract: Recent analysis demonstrates that the HIV-1 Long Terminal Repeat (HIV LTR) promoter exhibits a range of possible transcriptional burst sizes and frequencies for any mean-expression level. However, these results have also been interpreted as demonstrating that cell-to-cell expression variability (noise) and mean are uncorrelated, a significant deviation from previous results. Here, we re-examine the available mRNA and protein abundance data for the HIV LTR and find that noise in mRNA and protein expression scales inversely with the mean along analytically predicted transcriptional burst-size manifolds. We then experimentally perturb transcriptional activity to test a prediction of the multiple burst-size model: that increasing burst frequency will cause mRNA noise to decrease along given burst-size lines as mRNA levels increase. The data show that mRNA and protein noise decrease as mean expression increases, supporting the canonical inverse correlation between noise and mean.
Source: PLoS ONE
Institutions: University of Illinois Urbana-Champaign, Carl R. Woese Institute for Genomic Biology, University of Pennsylvania, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, University of Delaware, Rockefeller University, Oak Ridge National Laboratory, Center for Nanophase Materials Sciences, University of Tennessee at Knoxville, Gladstone Institutes, Lawrence Berkeley National Laboratory, University of California, San Francisco, University of California, Berkeley
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: Molecular Biophysics Training Grant, Developing Transmissible Antivirals by Exploiting Gene-Expression Circuitry, Stochastic Gene Expression in Retroviral Latency, A Comprehensive Spatial Picture of Transcription in the Nucleus, Rapid and highly sensitive influenza detection with RNA FISH, G6671297155, G7538388732, Screening for modulators of Tat positive feedback for biasing HIV latency, G8543390763, CAREER: Unraveling homeostatic mechanisms in gene expression regulation: Integrating research and scientific communication
OpenAlex ID: W2951941730