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DOE OSTI · 2567061

Altering translation allows E. coli to overcome G-quadruplex stabilizers

Cueny, Rachel R. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000273886864)·Voter, Andrew F. [University of Wisconsin-Madison, WI (United States)]·McKenzie, Aidan M. [University of Wisconsin-Madison, WI (United States)]·Morgenstern, Marcel [University of Wisconsin-Madison, WI (United States)]·Myers, Kevin S. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000333023877)·Place, Michael M. [University of Wisconsin-Madison, WI (United States)]·Peters, Jason M. [University of Wisconsin-Madison, WI (United States)]·Coon, Joshua J. [University of Wisconsin-Madison, WI (United States); Morgridge Institute for Research, Madison, WI (United States)]·Keck, James L. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000259610220)
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Abstract

G-quadruplex (G4) structures can form in guanine-rich DNA or RNA and have been found to modulate cellular processes, including replication, transcription, and translation. Many studies on the cellular roles of G4s have focused on eukaryotic systems, with far fewer probing bacterial G4s. Using a chemical-genetic approach, we identified genes in Escherichia coli that are important for growth in G4-stabilizing conditions. Reducing levels of translation elongation factor Tu or slowing translation initiation or elongation with kasugamycin, chloramphenicol, or spectinomycin suppress the effects of G4-stabilizing compounds. In contrast, reducing the expression of specific translation termination or ribosome recycling proteins is detrimental to growth in G4-stabilizing conditions. Proteomic and transcriptomic analyses reveal decreased protein and transcript levels, respectively, for ribosome assembly factors and proteins associated with translation in the presence of G4 stabilizer. Our results support a model in which reducing the rate of translation by altering translation initiation, translation elongation, or ribosome assembly can compensate for G4-related stress in E. coli.

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Cueny, Rachel R. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000273886864), Voter, Andrew F. [University of Wisconsin-Madison, WI (United States)], McKenzie, Aidan M. [University of Wisconsin-Madison, WI (United States)], Morgenstern, Marcel [University of Wisconsin-Madison, WI (United States)], Myers, Kevin S. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000333023877), Place, Michael M. [University of Wisconsin-Madison, WI (United States)], Peters, Jason M. [University of Wisconsin-Madison, WI (United States)], Coon, Joshua J. [University of Wisconsin-Madison, WI (United States); Morgridge Institute for Research, Madison, WI (United States)], Keck, James L. [University of Wisconsin-Madison, WI (United States)] (ORCID:0000000259610220). 2025-04-07. Altering translation allows E. coli to overcome G-quadruplex stabilizers. https://doi.org/10.1093/nar%2Fgkaf264

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