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Principles of cellular resource allocation revealed by condition-dependent proteome profiling

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TLDR
It is suggested that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate, which is currently the limit of full ribosomal usage.
Abstract
Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of non-ribosomal proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce excess ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells does not contribute to translation. Further, this fraction increases as growth rate decreases and these excess ribosomal proteins are employed when translation demands unexpectedly increase. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.

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Journal ArticleDOI

Homeostasis of protein and mRNA concentrations in growing cells

TL;DR: A minimal gene expression model is constructed that predicts a transition from exponential to linear growth of cell volume as the protein-to-DNA ratio increases and shows that this result emerges naturally when ribosomes and RNAPs limit expression.
Journal ArticleDOI

Root of the Tree: The Significance, Evolution, and Origins of the Ribosome.

TL;DR: The ribosome shows that protein folding initiated with intrinsic disorder, supported through a short, primitive exit tunnel, and was enabled by a long, mature exit tunnel that partially offset the general thermodynamic tendency of all polypeptides to form β-sheets.
Journal ArticleDOI

Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions.

TL;DR: Bacteria tune ribosome usage across different limiting nutrients to enable balanced nutrient-limited growth while also preparing for future nutrient upshifts.
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Small and Large Ribosomal Subunit Deficiencies Lead to Distinct Gene Expression Signatures that Reflect Cellular Growth Rate

TL;DR: Two distinct signatures of protein synthesis suggest intriguing and currently mysterious differences in the cellular consequences of deficiency for small and large ribosomal subunits.
Journal ArticleDOI

Proteotoxicity from aberrant ribosome biogenesis compromises cell fitness

TL;DR: It is proposed that ribosome assembly is a key vulnerability of proteostasis maintenance in proliferating cells that may be compromised by diverse genetic, environmental, and xenobiotic perturbations that generate orphan r-proteins.
References
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TL;DR: A statistical model is presented to estimate the accuracy of peptide assignments to tandem mass (MS/MS) spectra made by database search applications such as SEQUEST, demonstrating that the computed probabilities are accurate and have high power to discriminate between correctly and incorrectly assigned peptides.
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Journal ArticleDOI

Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications.

TL;DR: A set of yeast strains based on Saccharomyces cerevisiae S288C in which commonly used selectable marker genes are deleted by design based on the yeast genome sequence has been constructed and analysed and will reduce plasmid integration events which can interfere with a wide variety of molecular genetic applications.
Book ChapterDOI

Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method

TL;DR: In this chapter the authors have provided instructions for transforming yeast by a number of variations of the LiAc/SS-DNA/PEG method to generate large numbers of transformants or deliver DNA constructs or oligonucleotides into the yeast cell.
Journal ArticleDOI

Bacterial Persistence as a Phenotypic Switch

TL;DR: Investigating the persistence of single cells of Escherichia coli with the use of microfluidic devices found phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates, leading to a simple mathematical description of the persistence switch.
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What are the fundamental principles of cell biology and cell growth?

The provided paper is about the principles of cellular resource allocation in budding yeast. It does not specifically address the fundamental principles of cell biology and cell growth.