RNA Polymerase II cluster dynamics predict mRNA output in living cells

Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synth...

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Autores principales: Cho, Won-Ki, Jayanth, Namrata, English, Brian P, Inoue, Takuma, Andrews, J Owen, Conway, William, Grimm, Jonathan B, Spille, Jan-Hendrik, Lavis, Luke D, Lionnet, Timothée, Cisse, Ibrahim I
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Biophysics and Structural Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929003/
https://www.ncbi.nlm.nih.gov/pubmed/27138339
http://dx.doi.org/10.7554/eLife.13617
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author Cho, Won-Ki
Jayanth, Namrata
English, Brian P
Inoue, Takuma
Andrews, J Owen
Conway, William
Grimm, Jonathan B
Spille, Jan-Hendrik
Lavis, Luke D
Lionnet, Timothée
Cisse, Ibrahim I
author_facet Cho, Won-Ki
Jayanth, Namrata
English, Brian P
Inoue, Takuma
Andrews, J Owen
Conway, William
Grimm, Jonathan B
Spille, Jan-Hendrik
Lavis, Luke D
Lionnet, Timothée
Cisse, Ibrahim I
author_sort Cho, Won-Ki
collection PubMed
description Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output. DOI: http://dx.doi.org/10.7554/eLife.13617.001
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spelling pubmed-49290032016-07-05 RNA Polymerase II cluster dynamics predict mRNA output in living cells Cho, Won-Ki Jayanth, Namrata English, Brian P Inoue, Takuma Andrews, J Owen Conway, William Grimm, Jonathan B Spille, Jan-Hendrik Lavis, Luke D Lionnet, Timothée Cisse, Ibrahim I eLife Biophysics and Structural Biology Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output. DOI: http://dx.doi.org/10.7554/eLife.13617.001 eLife Sciences Publications, Ltd 2016-05-03 /pmc/articles/PMC4929003/ /pubmed/27138339 http://dx.doi.org/10.7554/eLife.13617 Text en © 2016, Cho et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Cho, Won-Ki
Jayanth, Namrata
English, Brian P
Inoue, Takuma
Andrews, J Owen
Conway, William
Grimm, Jonathan B
Spille, Jan-Hendrik
Lavis, Luke D
Lionnet, Timothée
Cisse, Ibrahim I
RNA Polymerase II cluster dynamics predict mRNA output in living cells
title RNA Polymerase II cluster dynamics predict mRNA output in living cells
title_full RNA Polymerase II cluster dynamics predict mRNA output in living cells
title_fullStr RNA Polymerase II cluster dynamics predict mRNA output in living cells
title_full_unstemmed RNA Polymerase II cluster dynamics predict mRNA output in living cells
title_short RNA Polymerase II cluster dynamics predict mRNA output in living cells
title_sort rna polymerase ii cluster dynamics predict mrna output in living cells
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929003/
https://www.ncbi.nlm.nih.gov/pubmed/27138339
http://dx.doi.org/10.7554/eLife.13617
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