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bioRxiv · 10.1101/2021.05.17.444432

Nuclear RNA concentration coordinates RNA production with cell size in human cells

Berry, S.·Müller, M.·Pelkmans, L.
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Abstract

Unlike its DNA template, RNA abundance and synthesis rates increase with cell size, as part of a mechanism of cellular RNA concentration homeostasis. Here, we study this scaling phenomenon in human cells by combining genome-wide perturbations with quantitative single-cell measurements. Despite relative ease in perturbing RNA synthesis, we find that RNA concentrations remain highly constant. Systems-level analysis indicates that perturbations that would lead to increased nuclear mRNA abundance result in downregulation of mRNA synthesis. This is associated with reduced levels of several transcription-associated proteins and protein states that are normally coordinated with RNA production in single cells, including RNA polymerase II (Pol II) itself. Acute shut-down of nuclear RNA degradation, elevation of nuclear mRNA levels, and mathematical modelling indicate that mammalian cells achieve RNA concentration homeostasis by an mRNA-based negative feedback on transcriptional activity in the nucleus. Ultimately, this acts to robustly scale Pol II abundance with cell volume and coordinate mRNA synthesis and degradation.

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Berry, S., Müller, M., Pelkmans, L.. 2021-05-17. Nuclear RNA concentration coordinates RNA production with cell size in human cells. https://doi.org/10.1101/2021.05.17.444432

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