Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels
Date
2016-07-28
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Public Library Science
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-tocell expression variability (noise) and mean are uncorrelated, a significant Developmentiation 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-sizemanifolds. 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.
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Dar, R. D., Shaffer, S. M., Singh, A., Razooky, B. S., Simpson, M. L., Raj, A., & Weinberger, L. S. (2016). Transcriptional bursting explains the noise-versus-mean relationship in mRNA and protein levels. Plos One, 11(7), e0158298. doi:10.1371/journal.pone.0158298