How total mRNA influences cell growth

BioRxiv

bioRxiv Subject Collection: Systems Biology
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How total mRNA influences cell growth

While the conventional wisdom is that growth rate is prominently set by ribosome amounts, in many biologically relevant situations the levels of mRNA and RNA polymerase can become a bottleneck for growth. Here, we construct a quantitative model of biosynthesis providing testable predictions for these situations. Assuming that RNA polymerases compete for genes and ribosomes for transcripts, the model gives general expressions relating growth rate, mRNA concentrations, ribosome and RNAP levels. On general grounds, the model predicts how the fraction of ribosomes in the proteome depends on total mRNA concentration, and inspects an underexplored regime in which the trade-off between transcript levels and ribosome abundances sets the cellular growth rate. In particular, we show that the model predicts and clarifies three important experimental observations, in budding yeast and E. coli bacteria: (i) that the growth-rate cost of unneeded protein expression can be affected by mRNA levels, (ii) that resource optimization leads to decreasing trends in mRNA levels at slow growth, and (iii) that ribosome allocation may increase, stay constant, or decrease, in response to transcription-inhibiting antibiotics.
Calabrese, L., Ciandrini, L., Cosentino Lagomarsino, M.
March 22, 2023
http://biorxiv.org/cgi/content/short/2023.03.17.533181v1?rss=1