Spurious regulatory connections dictate the expression‐fitness landscape of translation factors
Name
msb.202110302.pdf
Description
Published version
Size
2.88 MB
Format
Adobe PDF
Checksum (MD5)
6195e5175b45b080b0bcc8a521715d1c
Author(s)
Lalanne, Jean-Benoît
Parker, Darren J
Li, Gene-Wei
Date Issued
2021
Journal
Molecular Systems Biology
Publisher
EMBO
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.15252/msb.202110302
