RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size

RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size
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RNA 聚合酶 II 动力学和 mRNA 稳定性反馈调节 mRNA 量与细胞大小的关系

DOI:
10.1016/j.cell.2023.10.012
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发表时间:
2023
期刊:
影响因子:
64.5
通讯作者:
Reyes-Lamothe, Rodrigo
Reyes-Lamothe, Rodrigo
中科院分区:
生物学1区
文献类型:
--
作者:
Swaffer, Matthew P.;Marinov, Georgi K.;Zheng, Huan;Fuentes Valenzuela, Lucas;Tsui, Crystal Yee;Jones, Andrew W.;Greenwood, Jessica;Kundaje, Anshul;Greenleaf, William J.;Reyes-Lamothe, Rodrigo

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细胞生长的一个基本特征是总蛋白和 RNA 的量随着细胞大小的增加而增加,以保持浓度大致恒定。其中一个关键组成部分是较大细胞中的整体转录率增加。在这里,我们将 RNA 聚合酶 II (RNAPII) 确定为芽殖酵母中 mRNA 转录随细胞大小变化的限制因素,因为转录对 RNAPII 的剂量高度敏感,但对转录机制的其他组件不敏感。我们的实验支持动态平衡模型,其中给定大小的全局 RNAPII 转录是由未接合的核质 RNAPII 与基因组的大规模作用招募动力学设定的。然而,这只会导致转录随大小的亚线性增加,然后随着细胞增大,mRNA 衰减率的降低会部分补偿这一增加。因此,限制 RNAPII 和 mRNA 稳定性反馈协同作用,可以根据细胞大小调整 mRNA 量。
A fundamental feature of cellular growth is that total protein and RNA amounts increase with cell size to keep concentrations approximately constant. A key component of this is that global transcription rates increase in larger cells. Here, we identify RNA polymerase II (RNAPII) as the limiting factor scaling mRNA transcription with cell size in budding yeast, as transcription is highly sensitive to the dosage of RNAPII but not to other components of the transcriptional machinery. Our experiments support a dynamic equilibrium model where global RNAPII transcription at a given size is set by the mass action recruitment kinetics of unengaged nucleoplasmic RNAPII to the genome. However, this only drives a sub-linear increase in transcription with size, which is then partially compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to scale mRNA amounts with cell size.
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