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Live-cell MS2 imaging of RAB7A and RHOA genes showed that burst size increases in proportion to cell size. Decomposing burst size revealed that this scaling originates primarily from longer ON times — once activated, promoters in larger cells remain active for longer. Burst amplitude stayed relatively constant, and inactive periods between bursts were only modestly shortened.

RNAseq of CCND1-manipulated cells yielded a Pearson R of 0.74 between mRNA and protein fold changes across cell size — substantially higher than the R = 0.29 from earlier size-sorted experiments. Most of the explanatory power for protein concentration changes comes from transcriptome changes rather than protein turnover.

SLAMseq revealed that individual mRNA half-lives do not differentially change across cell sizes. A mild global stabilization of mRNA was observed in larger cells — consistent with a RNA concentration homeostatic mechanism seen in yeast — but this was uniform across transcripts rather than gene-specific, and did not correlate with mRNA size-slope values.

TMT mass spectrometry of CCND1 manipulated cells revealed that the majority of the proteome scales with cell size, as previously seen for size-sorted cells. In addition, we also showed by sorting cells of different sizes and different cell cycle state that this remodeling of the proteome is not strongly influenced by the cell cycle.

Pulse SILAC-TMT measurements showed that protein half-lives are mostly constant across a two-fold cell size increase. For short-lived proteins, a small but significant correlation with protein size-slope was found — meaning protein turnover for unstable proteins may make a minor contribution to size-dependent proteome remodeling.

When lysosome function was challenged with LLoMe, large cells showed significantly higher rates of cell death than small cells. A longer treatment with chloroquine produced a similar, though more modest, size-dependent increase in death. This effect was specific to lysosomes — treatment with the proteasome inhibitor bortezomib produced the opposite result, with smaller cells being more vulnerable.