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A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability

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 under...

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Autores principales: Felletti, Michele, Romilly, Cédric, Wagner, E Gerhart H, Jonas, Kristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443254/
https://www.ncbi.nlm.nih.gov/pubmed/34524083
http://dx.doi.org/10.7554/eLife.71611
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author Felletti, Michele
Romilly, Cédric
Wagner, E Gerhart H
Jonas, Kristina
author_facet Felletti, Michele
Romilly, Cédric
Wagner, E Gerhart H
Jonas, Kristina
author_sort Felletti, Michele
collection PubMed
description 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.
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spelling pubmed-84432542021-09-17 A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability Felletti, Michele Romilly, Cédric Wagner, E Gerhart H Jonas, Kristina eLife Chromosomes and Gene Expression 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. eLife Sciences Publications, Ltd 2021-09-15 /pmc/articles/PMC8443254/ /pubmed/34524083 http://dx.doi.org/10.7554/eLife.71611 Text en © 2021, Felletti et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Felletti, Michele
Romilly, Cédric
Wagner, E Gerhart H
Jonas, Kristina
A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title_full A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title_fullStr A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title_full_unstemmed A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title_short A nascent polypeptide sequence modulates DnaA translation elongation in response to nutrient availability
title_sort nascent polypeptide sequence modulates dnaa translation elongation in response to nutrient availability
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443254/
https://www.ncbi.nlm.nih.gov/pubmed/34524083
http://dx.doi.org/10.7554/eLife.71611
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