RNA Polymerase II cluster dynamics predict mRNA output in living cells
RNA Polymerase II cluster dynamics predict mRNA output in living cells
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DOI：
10.7554/elife.13617
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发表时间：
2016-05-03
期刊：
影响因子：
7.7
通讯作者：
Cisse, Ibrahim I.
中科院分区：
文献类型：
--
作者：
Cho, Won-Ki;Jayanth, Namrata;Cisse, Ibrahim I.
蛋白质聚类是哺乳动物细胞基因组调控的一个标志。然而，所涉及的动态分子过程使得很难将聚类与体内功能后果联系起来。我们开发了一种活细胞超分辨率方法来揭示mRNA合成与基因位点上RNA聚合酶II（Pol II）簇动力学之间的相关性。对于小鼠胚胎成纤维细胞中的内源性β -肌动蛋白基因，我们观察到短寿命（类似于8秒）Pol II簇与基础mRNA输出相关。在血清刺激期间，Pol II簇寿命的典型增加与合成mrna数量的成比例增加相关。我们的研究结果表明，Pol II的瞬时聚集可能构成转录前调控事件，可预测地调节新生mRNA的输出。
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 beta-actin genes in mouse embryonic fibroblasts, we observe that short-lived (similar to 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.