Gene expression in growing cells: A biophysical primer

ArXiv [Preprint]. 2023 Nov 20:arXiv:2311.12143v1.

Abstract

Cell growth and gene expression, two essential elements of all living systems, have long been the focus of biophysical interrogation. Advances in experimental single-cell methods have invigorated theoretical studies into these processes. However, until recently, there was little dialog between the two areas of study. In particular, most theoretical models for gene regulation assumed gene activity to be oblivious to the progression of the cell cycle between birth and division. But, in fact, there are numerous ways in which the periodic character of all cellular observables can modulate gene expression. The molecular factors required for transcription and translation-RNA polymerase, transcription factors, ribosomes-increase in number during the cell cycle, but are also diluted due to the continuous increase in cell volume. The replication of the genome changes the dosage of those same cellular players but also provides competing targets for regulatory binding. Finally, cell division reduces their number again, and so forth. Stochasticity is inherent to all these biological processes, manifested in fluctuations in the synthesis and degradation of new cellular components as well as the random partitioning of molecules at each cell division event. The notion of gene expression as stationary is thus hard to justify. In this review, we survey the emerging paradigm of cell-cycle regulated gene expression, with an emphasis on the global expression patterns rather than gene-specific regulation. We discuss recent experimental reports where cell growth and gene expression were simultaneously measured in individual cells, providing first glimpses into the coupling between the two, and motivating several questions. How do the levels of gene expression products - mRNA and protein - scale with the cell volume and cell-cycle progression? What are the molecular origins of the observed scaling laws, and when do they break down to yield non-canonical behavior? What are the consequences of cell-cycle dependence for the heterogeneity ("noise") in gene expression within a cell population? While the experimental findings, not surprisingly, differ among genes, organisms, and environmental conditions, several theoretical models have emerged that attempt to reconcile these differences and form a unifying framework for understanding gene expression in growing cells.

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  • Preprint