美国斯坦福大学Jan M. Skotheim研究组揭示了RNA聚合酶II动力学和mRNA稳定性反馈衡量mRNA数量随细胞大小的变化。这一研究成果发表在2023年11月8日出版的国际学术期刊《细胞》上。

他们确定RNA聚合酶II (RNAPII)是出芽酵母中mRNA转录随细胞大小变化的限制因子，因为转录对RNAPII的剂量高度敏感，而对转录机制的其他成分不敏感。他们的实验支持一个动态平衡模型，其中给定大小的全局RNAPII转录是由未参与的核质RNAPII，向基因组的质量作用招募动力学决定的。

然而，这只会导致转录随细胞大小的亚线性增长，然后随着细胞的扩大，mRNA衰减率的降低部分补偿了这一增长。因此，限制RNAPII和对mRNA稳定性的反馈协同工作，使mRNA的数量随细胞大小而增加。

据介绍，细胞生长的一个基本特征是总蛋白质和RNA的数量随着细胞大小的增加而增加，以保持浓度大致恒定。其中一个关键因素是，在较大的细胞中，整体转录率会增加。

附：英文原文

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

Author: Matthew P. Swaffer, Georgi K. Marinov, Huan Zheng, Lucas Fuentes Valenzuela, Crystal Yee Tsui, Andrew W. Jones, Jessica Greenwood, Anshul Kundaje, William J. Greenleaf, Rodrigo Reyes-Lamothe, Jan M. Skotheim

Issue&Volume: 2023-11-08

Abstract: A fundamental feature of cellular growth is that total protein and RNA amounts increasewith cell size to keep concentrations approximately constant. A key component of thisis that global transcription rates increase in larger cells. Here, we identify RNApolymerase II (RNAPII) as the limiting factor scaling mRNA transcription with cellsize in budding yeast, as transcription is highly sensitive to the dosage of RNAPIIbut not to other components of the transcriptional machinery. Our experiments supporta dynamic equilibrium model where global RNAPII transcription at a given size is setby the mass action recruitment kinetics of unengaged nucleoplasmic RNAPII to the genome.However, this only drives a sub-linear increase in transcription with size, whichis 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 mRNAamounts with cell size.

DOI: 10.1016/j.cell.2023.10.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01128-5