title: Transcriptional Bursting Explains the Noise-Versus-Mean Relationship in mRNA and Protein Levels.
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.
authors.affiliation: Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois, United States of America.|Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.|Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Roy D
authors.initials: RD
authors.lastname: Dar
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Sydney M
authors.initials: SM
authors.lastname: Shaffer
authors.affiliation: Department of Electrical and Computer Engineering, University of Delaware, Newark, Delaware, United States of America.
authors.forename: Abhyudai
authors.initials: A
authors.lastname: Singh
authors.affiliation: Rockefeller University, New York, New York, United States of America.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Razooky
authors.affiliation: Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.|Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Knoxville, Tennessee, United States of America.|Department of Materials Science and Engineering, University of Tennessee, Knoxville, Knoxville, Tennessee, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Simpson
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Arjun
authors.initials: A
authors.lastname: Raj
authors.affiliation: Gladstone Institute (Virology and Immunology), San Francisco, California, United States of America.|Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Leor S
authors.initials: LS
authors.lastname: Weinberger
mesh_terms: D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins