Spurious regulatory connections dictate the expression-fitness landscape of translation factors

Autor: Darren J. Parker, Gene-Wei Li, Jean-Benoît Lalanne
Rok vydání: 2021
Předmět:
Medicine (General)
Proteome
Transcription
Genetic
Fitness landscape
QH301-705.5
Computational biology
Bacillus subtilis
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Transcriptome
03 medical and health sciences
0302 clinical medicine
R5-920
Bacterial Proteins
Stress
Physiological
translation factors
peptide chain release factors
Biology (General)
Spurious relationship
030304 developmental biology
0303 health sciences
General Immunology and Microbiology
Base Sequence
Cell growth
multiscale measurements
Applied Mathematics
Translation (biology)
Gene Expression Regulation
Bacterial
Articles
Protein Biosynthesis & Quality Control
biology.organism_classification
Stop codon
Computational Theory and Mathematics
Expression (architecture)
expression‐fitness landscape
regulatory entrenchment
Protein Biosynthesis
CRISPR-Cas Systems
General Agricultural and Biological Sciences
Synthetic Biology & Biotechnology
030217 neurology & neurosurgery
Genome
Bacterial
Information Systems
Peptide Termination Factors
Zdroj: Molecular Systems Biology
Molecular Systems Biology, Vol 17, Iss 4, Pp n/a-n/a (2021)
ISSN: 1744-4292
Popis: 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.
Quantitative multiscale measurements of the responses to varied expression of translation termination factors in Bacillus subtilis reveal ‘regulatory entrenchment’, whereby expression‐fitness landscapes are dictated by idiosyncratic interactions in the regulatory network.
Databáze: OpenAIRE
Externí odkaz: