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Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels
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 (noi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965078/ https://www.ncbi.nlm.nih.gov/pubmed/27467384 http://dx.doi.org/10.1371/journal.pone.0158298 |
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author | Dar, Roy D. Shaffer, Sydney M. Singh, Abhyudai Razooky, Brandon S. Simpson, Michael L. Raj, Arjun Weinberger, Leor S. |
author_facet | Dar, Roy D. Shaffer, Sydney M. Singh, Abhyudai Razooky, Brandon S. Simpson, Michael L. Raj, Arjun Weinberger, Leor S. |
author_sort | Dar, Roy D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4965078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49650782016-08-18 Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels Dar, Roy D. Shaffer, Sydney M. Singh, Abhyudai Razooky, Brandon S. Simpson, Michael L. Raj, Arjun Weinberger, Leor S. PLoS One Research Article 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. Public Library of Science 2016-07-28 /pmc/articles/PMC4965078/ /pubmed/27467384 http://dx.doi.org/10.1371/journal.pone.0158298 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Dar, Roy D. Shaffer, Sydney M. Singh, Abhyudai Razooky, Brandon S. Simpson, Michael L. Raj, Arjun Weinberger, Leor S. Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title | Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title_full | Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title_fullStr | Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title_full_unstemmed | Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title_short | Transcriptional Bursting Explains the Noise–Versus–Mean Relationship in mRNA and Protein Levels |
title_sort | transcriptional bursting explains the noise–versus–mean relationship in mrna and protein levels |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965078/ https://www.ncbi.nlm.nih.gov/pubmed/27467384 http://dx.doi.org/10.1371/journal.pone.0158298 |
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