Resilience and proteome response of Escherichia coli to high levels of isoleucine mistranslation

Accurate pairing of amino acids and tRNAs is a prerequisite for faithful translation of genetic information during protein biosynthesis. Here we present the effects of proteome-wide mistranslation of isoleucine (Ile) by canonical valine (Val) or non-proteinogenic norvaline (Nva) in a genetically eng...

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Published in:International journal of biological macromolecules 2024-03, Vol.262 (Pt 1), p.130068-130068, Article 130068
Main Authors: Pranjic, Marija, Spät, Philipp, Semanjski Curkovic, Maja, Macek, Boris, Gruic-Sovulj, Ita, Mocibob, Marko
Format: Article
Language:English
Subjects:
Chaperone
Escherichia coli - genetics
Escherichia coli - metabolism
Isoleucine
Isoleucine-tRNA Ligase - chemistry
Isoleucine-tRNA Ligase - genetics
Isoleucine-tRNA Ligase - metabolism
Isoleucyl-tRNA synthetase
Mistranslation
Norvaline
Protein Aggregates
Protein aggregation
Proteome - metabolism
Resilience, Psychological
RNA, Transfer - genetics
RNA, Transfer - metabolism
Valine
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Summary:Accurate pairing of amino acids and tRNAs is a prerequisite for faithful translation of genetic information during protein biosynthesis. Here we present the effects of proteome-wide mistranslation of isoleucine (Ile) by canonical valine (Val) or non-proteinogenic norvaline (Nva) in a genetically engineered Escherichia coli strain with an editing-defective isoleucyl-tRNA synthetase (IleRS). Editing-defective IleRS efficiently mischarges both Val and Nva to tRNAIle and impairs the translational accuracy of Ile decoding. When mistranslation was induced by the addition of Val or Nva to the growth medium, an Ile-to-Val or Ile-to-Nva substitution of up to 20 % was measured by high-resolution mass spectrometry. This mistranslation level impaired bacterial growth, promoted the SOS response and filamentation during stationary phase, caused global proteome dysregulation and upregulation of the cellular apparatus for maintaining proteostasis, including the major chaperones (GroES/EL, DnaK/DnaJ/GrpE and HtpG), the disaggregase ClpB and the proteases (Lon, HslV/HslU, ClpA, ClpS). The most important consequence of mistranslation appears to be non-specific protein aggregation, which is effectively counteracted by the disaggregase ClpB. Our data show that E. coli can sustain high isoleucine mistranslation levels and remain viable despite excessive protein aggregation and severely impaired translational fidelity. However, we show that inaccurate translation lowers bacterial resilience to heat stress and decreases bacterial survival at elevated temperatures. [Display omitted] •Escherichia coli is resilient to unexpectedly high levels of isoleucine mistranslation.•Translational errors increase protein aggregation, and demand for chaperone-assisted protein folding and degradation.•Excessive protein aggregation is efficiently counteracted by cellular disaggregase.•Biological process most compromised by mistranslation is protein translation.•Isoleucine mistranslation inhibits the division of E. coli cells in the stationary phase.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2024.130068