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Title: Transcriptional bursting explains the noise–versus–mean relationship in mRNA and protein levels

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [4];  [5];  [2];  [6]
  1. Univ. of Illinois Urbana-Champaign, Urbana, IL (United States)
  2. Univ. of Pennsylvania, Philadelphia, PA (United States)
  3. Univ. of Delaware, Newark, DE (United States)
  4. Rockefeller Univ., New York, NY (United States)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  6. Gladstone Institutes, San Francisco, CA (United States); Univ. of California San Francisco, San Francisco, CA (United States)
+ Show Author Affiliations

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-tocell 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. In conclusion, the data show that mRNA and protein noise decrease as mean expression increases, supporting the canonical inverse correlation between noise and mean.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Joint Institute for Biological Sciences (JIBS)
Sponsoring Organization:
USDOE Laboratory Directed Research and Development (LDRD) Program
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1279452
Journal Information:
PLoS ONE, Vol. 11, Issue 7; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 37 works
Citation information provided by
Web of Science

References (13)

Genetic Determinants and Cellular Constraints in Noisy Gene Expression journal December 2013
Markovian Modeling of Gene-Product Synthesis journal October 1995
Orthogonal control of expression mean and variance by epigenetic features at different genomic loci journal May 2015
Transcriptional Bursting from the HIV-1 Promoter Is a Significant Source of Stochastic Noise in HIV-1 Gene Expression journal April 2010
Lentiviral Vectors to Study Stochastic Noise in Gene Expression book January 2011
Transcriptional burst frequency and burst size are equally modulated across the human genome journal October 2012
Screening for noise in gene expression identifies drug synergies journal June 2014
HIV Promoter Integration Site Primarily Modulates Transcriptional Burst Size Rather Than Frequency journal September 2010
Stochastic mRNA Synthesis in Mammalian Cells journal September 2006
Imaging individual mRNA molecules using multiple singly labeled probes journal September 2008
Dynamics of protein noise can distinguish between alternate sources of gene‐expression variability journal January 2012
Stochasticity in Transcriptional Regulation: Origins, Consequences, and Mathematical Representations journal December 2001
Chance Fluctuations in mRNA Output in Mammalian Cells journal September 2006

Cited By (11)

Simulating multiple faceted variability in single cell RNA sequencing journal June 2019
What shapes eukaryotic transcriptional bursting? journal January 2017
Fine-tuning of noise in gene expression with nucleosome remodeling journal June 2018
Discontinuous transcription journal January 2018
3’-5’ crosstalk contributes to transcriptional bursting posted_content December 2020
Stochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency journal December 2019
Discontinuous transcription book December 2015
Stochastic transcription in the p53‐mediated response to DNA damage is modulated by burst frequency text January 2019
3 ′-5 ′ crosstalk contributes to transcriptional bursting journal February 2021
Cell Size-Based Decision-Making of a Viral Gene Circuit journal December 2018
Stochastic gene expression is optimized to drive developmental self-organization journal April 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV
messenger RNA
cloning
fluorescent in situ hybridization
gene expression
HIV-1
human genomics
protein expression