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Annu Rev Microbiol. 2021 Oct 08;75:243-267. doi: 10.1146/annurev-micro-041921-012646. Epub 2021 Aug 03.

Quantitative Control for Stoichiometric Protein Synthesis.

Annual review of microbiology

James C Taggart, Jean-BenoƮt Lalanne, Gene-Wei Li

Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email: [email protected], [email protected].
  2. Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  3. Current affiliation: Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; email: [email protected].

PMID: 34343023 DOI: 10.1146/annurev-micro-041921-012646

Abstract

Bacterial protein synthesis rates have evolved to maintain preferred stoichiometries at striking precision, from the components of protein complexes to constituents of entire pathways. Setting relative protein production rates to be well within a factor of two requires concerted tuning of transcription, RNA turnover, and translation, allowing many potential regulatory strategies to achieve the preferred output. The last decade has seen a greatly expanded capacity for precise interrogation of each step of the central dogma genome-wide. Here, we summarize how these technologies have shaped the current understanding of diverse bacterial regulatory architectures underpinning stoichiometric protein synthesis. We focus on the emerging expanded view of bacterial operons, which encode diverse primary and secondary mRNA structures for tuning protein stoichiometry. Emphasis is placed on how quantitative tuning is achieved. We discuss the challenges and open questions in the application of quantitative, genome-wide methodologies to the problem of precise protein production.

Keywords: differential RNA stability; differential translation; expression stoichiometry; operon mRNA isoform; proportional synthesis

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