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

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 fact...

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Bibliographic Details
Published in:Cell 2023-11, Vol.186 (24), p.5254-5268.e26
Main Authors: 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, Skotheim, Jan M.
Format: Article
Language:English
Subjects:
cell biology
Cell Size
Feedback
RNA
RNA biology
RNA polymerase II
RNA Polymerase II - metabolism
RNA Stability
RNA, Messenger - genetics
RNA, Messenger - metabolism
size scaling
systems biology
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Summary: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. [Display omitted] •Total mRNA must increase as a cell grows to ensure concentration homeostasis•RNAPII is the major dosage-limiting component of the transcriptional machinery in yeast•The size-dependent increase in RNAPII-DNA binding follows dynamic equilibrium kinetics•mRNA turnover decreases in larger cells to support mRNA concentration homeostasis mRNA transcription in budding yeast increases with cell size due to the equilibrium kinetics of dosage-limiting RNA polymerase II and the genome. This is then supported by a global increase in mRNA stability in larger cells to better scale mRNA amounts with cell size.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2023.10.012