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

Genome concentration limits cell growth and modulates proteome composition inEscherichia coli

“…Comparison with studies on eukaryotic cells suggests conservation of gene expression principles across domains of life. For instance, in yeast, it has been shown that the global transcription rate in G1-arrested cells is higher in diploids than haploids of similar sizes (Swaffer et al, 2023), consistent with DNA concentration being a limiting factor for transcription. Furthermore, in both yeast and mammalian cells, small G1-arrested cells display higher growth rate (or global RNA or protein synthesis rate) per cell volume than large ones that have exceeded a certain volume (Cadart et al, 2018; Liu et al, 2022; Neurohr et al, 2019; Zatulovskiy et al, 2022).…”

“…In yeast cells, an increase in RNAP II gene occupancy combined with a decrease in mRNA turnover helps mitigate DNA dilution on global transcription activities up to a certain cell volume beyond which the compensation breaks down (Swaffer et al, 2023; Zhurinsky et al, 2010). Such buffering activities, which are consistent with model predictions (Figure 4 – figure supplement 5) (Swaffer et al, 2023), may also be at play in bacteria, potentially in a growth medium-dependent manner.…”

“…In yeast cells, an increase in RNAP II gene occupancy combined with a decrease in mRNA turnover helps mitigate DNA dilution on global transcription activities up to a certain cell volume beyond which the compensation breaks down (Swaffer et al, 2023; Zhurinsky et al, 2010). Such buffering activities, which are consistent with model predictions (Figure 4 – figure supplement 5) (Swaffer et al, 2023), may also be at play in bacteria, potentially in a growth medium-dependent manner. For example, in our E. coli experiments, we noted that the global transcriptional activity (total amount of active RNAPs) strongly deviated from proportional scaling with cell size in 1N cells compared to WT and multi-N cells in all tested medium conditions (Figure 3H and Figure 3 – supplement 4G-H).…”

“…A combined genome file of E. coli K-12 MG1655 and C. crescentus NA1000 with gene annotations was generated using a previously described approach (Swaffer et al, 2023). Read mapping statistics and genome browser tracks were generated using custom Python scripts.…”

Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output

“…3, A and B, 'perfect compensation' model, light red). Alternatively, the degree of compensation may depend on the initial expression levels ('expression-dependent' model, dark red) if highly expressed genes are in a regime where their promoters are closer to a saturation kinetic due to the initially high occupancy of Pol II slowing the loading of additional Pol II (Swaffer et al, 2023). This limitation would cause more highly expressed transcripts to decrease in abundance relative to control ('expression-dependent' model, dark red).…”