Datasets

Title	Spurious regulatory connections dictate the expression-fitness landscape of translation factors
Organism
Number of Samples	12
Release Date	2020/11/25 00:00
Sequencing Types
Protocol Details

Title
Authors	Lalanne JB,Parker DJ,Li GW
Journal	Molecular systems biology
Publication Date	2021 Apr
Abstract	During steady-state cell growth, individual enzymatic fluxes can be directly inferred from growth rate by mass conservation, but the inverse problem remains unsolved. Perturbing the flux and expression of a single enzyme could have pleiotropic effects that may or may not dominate the impact on cell fitness. Here, we quantitatively dissect the molecular and global responses to varied expression of translation termination factors (peptide release factors, RFs) in the bacterium Bacillus subtilis. While endogenous RF expression maximizes proliferation, deviations in expression lead to unexpected distal regulatory responses that dictate fitness reduction. Molecularly, RF depletion causes expression imbalance at specific operons, which activates master regulators and detrimentally overrides the transcriptome. Through these spurious connections, RF abundances are thus entrenched by focal points within the regulatory network, in one case located at a single stop codon. Such regulatory entrenchment suggests that predictive bottom-up models of expression-fitness landscapes will require near-exhaustive characterization of parts. © 2021 The Authors. Published under the terms of the CC BY 4.0 license.
PMC	PMC8073009
PMID	33900014
DOI

Lalanne et al. 2020 (PRJNA680784)