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

Dar, Roy; Shaffer, Sydney M.; Singh, Abhyudai; Razooky, Brandon S.; Simpson, Michael L.; Raj, Arjun; Weinberger, Leor S.

doi:10.1371/journal.pone.0158298

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

Journal Article · Thu Jul 28 00:00:00 EDT 2016 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0158298· OSTI ID:1279452

Dar, Roy ^[1]; Shaffer, Sydney M. ^[2]; Singh, Abhyudai ^[3]; Razooky, Brandon S. ^[4]; Simpson, Michael L. ^[5]; Raj, Arjun ^[2]; Weinberger, Leor S. ^[6]

Univ. of Illinois Urbana-Champaign, Urbana, IL (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States)
Univ. of Delaware, Newark, DE (United States)
Rockefeller Univ., New York, NY (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
Gladstone Institutes, San Francisco, CA (United States); Univ. of California San Francisco, San Francisco, CA (United States)

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:: ORNL Program Development; USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1279452

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 7 Vol. 11; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Discontinuous transcription Kahl, Günter The Dictionary of Genomics, Transcriptomics and Proteomics https://doi.org/10.1002/9783527678679.dg03152	book	December 2015
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References (14)

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