1. RNA Polymerase II cluster dynamics predict mRNA output in living cells
- Author
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Timothée Lionnet, Jan-Hendrik Spille, Ibrahim I Cisse, Brian P. English, Won-Ki Cho, Jonathan B. Grimm, Takuma Inoue, Luke D. Lavis, William Conway, Namrata Jayanth, J Owen Andrews, Massachusetts Institute of Technology. Department of Physics, Cho, Won-ki, Jayanth, Namrata, Andrews, James Owen, Conway, William E., Spille, Jan Hendrik, Cisse, Ibrahim I, and Inoue, Takuma
- Subjects
0301 basic medicine ,Transcription factories ,Mouse ,QH301-705.5 ,mRNA ,Science ,RNA polymerase II ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Transcription (biology) ,Gene expression ,Transcriptional regulation ,Animals ,RNA, Messenger ,Biology (General) ,Gene ,Cells, Cultured ,Messenger RNA ,General Immunology and Microbiology ,biology ,General Neuroscience ,General Medicine ,Fibroblasts ,Biophysics and Structural Biology ,Molecular biology ,Actins ,030104 developmental biology ,Gene Expression Regulation ,Genetic Loci ,Genes and Chromosomes ,biology.protein ,gene expression ,Medicine ,RNA Polymerase II ,Transcription factor II D ,bursting ,transcription ,030217 neurology & neurosurgery ,Research Article ,clustering - Abstract
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., National Cancer Institute (U.S.) (DP2CA195769)
- Published
- 2016