PT  - JOURNAL ARTICLE
AU  - Roy D. Dar
AU  - Sydney M. Schaffer
AU  - Siddarth S. Dey
AU  - Jonathan E. Foley
AU  - Abhyudai Singh
AU  - Brandon S. Razooky
AU  - Adam P. Arkin
AU  - David V. Schafer
AU  - Michael L. Simpson
AU  - Arjun Raj
AU  - Leor S. Weinberger
TI  - Transcriptional bursting explains the noise-versus-mean relationship in mRNA and protein levels
AID  - 10.1101/049528
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 049528
4099  - http://biorxiv.org/content/early/2016/04/21/049528.short
4100  - http://biorxiv.org/content/early/2016/04/21/049528.full
AB  - Recent analysis (Dey et al, 2015), 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.Conflict of Interest The authors declare that they have no conflict of interest.