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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Bibliographic Details
Main Authors: English, Brian P, Grimm, Jonathan B, Lavis, Luke D, Lionnet, Timothée, Cho, Won-ki, Jayanth, Namrata, Andrews, James Owen, Conway, William E., Spille, Jan Hendrik, Cisse, Ibrahim I, Inoue, Takuma
Other Authors: Massachusetts Institute of Technology. Department of Physics
Format: Article
Language:en_US
Published: eLife Sciences Publications, Ltd 2017
Online Access:http://hdl.handle.net/1721.1/108356
https://orcid.org/0000-0001-9336-0686
https://orcid.org/0000-0001-9746-6007
https://orcid.org/0000-0003-1867-4380
https://orcid.org/0000-0001-8493-4721
https://orcid.org/0000-0002-8764-1809
https://orcid.org/0000-0003-0362-0072
Description
Summary: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.