Growth-Optimized Aminoacyl-tRNA Synthetase Levels Prevent Maximal tRNA Charging

Parker, Darren J.; Lalanne, Jean-Benoît; Kimura, Satoshi; Johnson, Grace E.; Waldor, Matthew K.; Li, Gene-Wei

doi:10.1016/j.cels.2020.07.005

Cited by 36 publications

(51 citation statements)

References 64 publications

(84 reference statements)

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“…S1d). These results suggest that RF expression is optimized for exponential phase growth, akin to the expression of several other factors (Dekel and Alon, 2005; Ehrenberg and Kurland, 1984; Li et al, 2014; Parker et al, 2020), and is consistent with the tight evolutionary conservation of expression stoichiometry in biological pathways (Lalanne et al, 2018).…”

Section: Resultssupporting

confidence: 71%

“…Abrogation of this effect following sigB deletion (Fig. 3d-e, S3f-g, dashed arrow) highlights that physiological trajectories can be modulated by individual regulatory proteins, as has been also demonstrated for tRNA synthetases and the stringent response in B. subtilis (Parker et al, 2020). However, unlike the stringent response, which is cognate to synthetase perturbation and beneficial to cell growth, the σ B response here is detrimental.…”

Section: Resultssupporting

confidence: 67%

“…Ribosome profiling further provided a high-resolution view of translation status in a subset of conditions. In order to precisely measure fitness, defined here as relative population growth rate in exponential phase, we designed a DNA-barcoded competition assay (Parker et al, 2020; Smith et al, 2009) with ±1% precision (±2σ, Fig. S2, Methods).…”

Section: Resultsmentioning

confidence: 99%

“…Predicting the shape of expression-fitness landscapes requires quantitative characterization of the cellular state at multiple levels. Although numerous expression-fitness landscapes have been previously mapped (Chou et al, 2014; Dekel and Alon, 2005; Duveau et al, 2017; Hawkins et al, 2019; Jost et al, 2020; Kavčič et al, 2019; Keren et al, 2016; Knöppel et al, 2016; Li et al, 2014; Palmer et al, 2018; Parker et al, 2020; Schober et al, 2019; Tubulekas and Hughes, 1993), these measurements rarely include concomitant assessment of the internal cell state following perturbations (but see (Jost et al, 2020; Parker et al, 2020)). With limited information bridging the molecular to cellular scales, the root causes of observed fitness defects are challenging to pinpoint (Fig.…”

Section: Introductionmentioning

confidence: 99%

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

Lalanne

Parker

2020

Preprint

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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 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.HighlightsPrecision measurements enable multiscale expression-to-fitness mapping.RF depletion leads to imbalanced translation for co-transcribed gene pairs.Imbalanced translation induces unintended regulons to the detriment of cell fitness.Swapping a single stop codon rewires global susceptibility to RF perturbation.

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Section: Resultssupporting

confidence: 71%

Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lalanne

Parker

2020

Preprint

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“…For matched Rend-seq/ribosome profiling datasets, strains were grown in LB or conditioned MCC medium (Parker et al 2020; Lalanne et al 2020) with various inducer (xylose, IPTG) concentrations (see Table S1). For these datasets, cells were grown in exponential phase for at least 10 doublings before harvesting at OD 600 ≈0.3.…”

Section: Methodsmentioning

confidence: 99%

Translational activation by an alternative sigma factor inBacillus subtilis

McCormick

Lalanne

Tct

et al. 2021

Preprint

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Sigma factors are an important class of bacterial transcription factors that lend specificity to RNA polymerases by binding to distinct promoter elements for genes in their regulons. Here we show that activation of the general stress sigma factor, σB, in Bacillus subtilis paradoxically leads to dramatic induction of translation for a subset of its regulon genes. These genes are translationally repressed when transcribed by the housekeeping sigma factor, σA, owing to extended RNA secondary structures as determined in vivo using DMS-MaPseq. Transcription from σB-dependent promoters liberates the secondary structures and activates translation, leading to dual induction. Translation efficiencies between σB- and σA-dependent RNA isoforms can vary by up to 100-fold, which in multiple cases exceeds the magnitude of transcriptional induction. These results highlight the role of long-range RNA folding in modulating translation and demonstrate that a transcription factor can regulate protein synthesis beyond its effects on transcript levels.

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Phytoplankton antioxidant systems and their contributions to cellular elemental stoichiometry

McCain

Bertrand

2021

Limnol Oceanogr Letters

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Oxidative stress plays a role in many aspects of cellular metabolism, and as a result, antioxidants have the potential to impact cellular stoichiometry and biogeochemical cycles. We reviewed how antioxidant systems influence macronutrient and micronutrient stoichiometry in marine phytoplankton and identified that antioxidant systems have important implications for micronutrient stoichiometry. By leveraging diatom proteomic data, we empirically estimated the level of micronutrient quota variation that can be attributed to antioxidant systems. Fe‐containing antioxidant expression may contribute to 3.3–10 μmol : mol variation in Fe : C, and superoxide dismutases appear to be important contributors to variation in Mn, Ni, Zn, and Cu quotas in phytoplankton. Critical next steps for the study of phytoplankton antioxidant systems are to (1) distinguish between oxidative stress and redox‐based gene regulation and (2) determine how antioxidants influence variation or consistency in micronutrient quotas under various environmental conditions.

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Growth-Optimized Aminoacyl-tRNA Synthetase Levels Prevent Maximal tRNA Charging

Cited by 36 publications

References 64 publications

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

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

Translational activation by an alternative sigma factor inBacillus subtilis

Phytoplankton antioxidant systems and their contributions to cellular elemental stoichiometry

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