Spurious regulatory connections dictate the expression-fitness landscape of translation factors
| العنوان: | Spurious regulatory connections dictate the expression-fitness landscape of translation factors |
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| المؤلفون: | Darren J. Parker, Gene-Wei Li, Jean-Benoît Lalanne |
| المصدر: | Molecular Systems Biology Molecular Systems Biology, Vol 17, Iss 4, Pp n/a-n/a (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1744-4292 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f51046bcd6554619b92dfce8c511d7d3 https://pubmed.ncbi.nlm.nih.gov/33900014 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f51046bcd6554619b92dfce8c511d7d3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17444292 |
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