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A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-2494-1345
Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-1469-4424
Number of Authors: 42021 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 10, article id e71611Article in journal (Refereed) Published
Abstract [en]

The ability to regulate DNA replication initiation in response to changing nutrient conditions is an important feature of most cell types. In bacteria, DNA replication is triggered by the initiator protein DnaA, which has long been suggested to respond to nutritional changes; nevertheless, the underlying mechanisms remain poorly understood. Here, we report a novel mechanism that adjusts DnaA synthesis in response to nutrient availability in Caulobacter crescentus. By performing a detailed biochemical and genetic analysis of the dnaA mRNA, we identified a sequence downstream of the dnaA start codon that inhibits DnaA translation elongation upon carbon exhaustion. Our data show that the corresponding peptide sequence, but not the mRNA secondary structure or the codon choice, is critical for this response, suggesting that specific amino acids in the growing DnaA nascent chain tune translational efficiency. Our study provides new insights into DnaA regulation and highlights the importance of translation elongation as a regulatory target. We propose that translation regulation by nascent chain sequences, like the one described, might constitute a general strategy for modulating the synthesis rate of specific proteins under changing conditions.

Place, publisher, year, edition, pages
2021. Vol. 10, article id e71611
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Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-197866DOI: 10.7554/eLife.71611ISI: 000696097100001PubMedID: 34524083OAI: oai:DiVA.org:su-197866DiVA, id: diva2:1604347
Available from: 2021-10-19 Created: 2021-10-19 Last updated: 2022-02-25Bibliographically approved

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Felletti, MicheleRomilly, CedricWagner, E. Gerhart H.Jonas, Kristina

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