Inhibiting translation elongation can aid genome duplication in Escherichia coli

Kamila K. Myka, Michelle Hawkins, Aisha H. Syeda, Milind K. Gupta, Caroline Meharg, Mark S. Dillingham, Nigel J. Savery, Robert G. Lloyd, Peter McGlynn*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
324 Downloads (Pure)

Abstract

Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking. Suppression depends on RelA-directed synthesis of (p)ppGpp, a signalling molecule that reduces replication-transcription conflicts, with RelA activation requiring ribosomal pausing. Levels of (p)ppGpp in these suppressors also correlate inversely with the need for Rho activity, an RNA translocase that can bind to emerging transcripts and displace transcription complexes. These data illustrate the fine balance between different mechanisms in facilitating gene expression and genome duplication and demonstrate that accessory helicases are a major determinant of this balance. This balance is also critical for other aspects of bacterial survival: the mutations identified here increase persistence indicating that similar mutations could arise in naturally occurring bacterial populations facing antibiotic challenge.
Original languageEnglish
Pages (from-to)2571-2584
Number of pages14
JournalNucleic Acids Research
Volume45
Issue number5
Early online date11 Dec 2016
DOIs
Publication statusPublished - 17 Mar 2017

Keywords

  • antibiotics
  • signal transduction
  • gene expression
  • mutation
  • amino acyl-trna synthetases
  • dna
  • dna-directed rna polymerase
  • genes
  • genome
  • guanosine tetraphosphate
  • proline
  • ribosomes
  • transfer rna
  • translating
  • rna
  • escherichia coli
  • chromosomal duplication
  • binding (molecular function)
  • molecule
  • complex

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    Myka, K. K., Hawkins, M., Syeda, A. H., Gupta, M. K., Meharg, C., Dillingham, M. S., Savery, N. J., Lloyd, R. G., & McGlynn, P. (2017). Inhibiting translation elongation can aid genome duplication in Escherichia coli. Nucleic Acids Research, 45(5), 2571-2584. https://doi.org/10.1093/nar/gkw1254