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Geneticin reduces mRNA stability.

Yavuz T Durmaz1, Alankrit Shatadal1, Kyle Friend1

  • 1Department of Chemistry and Biochemistry, Washington and Lee University, Lexington, Virginia, United States of America.

Plos One
|July 28, 2022
PubMed
Summary
This summary is machine-generated.

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Geneticin-G418, an antibiotic, decreases messenger RNA (mRNA) stability by interfering with optimal codons. This finding reveals how translation fidelity impacts mRNA decay and protein synthesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Messenger RNA (mRNA) translation is linked to mRNA decay, with ribosomes potentially initiating mRNA destruction.
  • mRNA features, like codon identity, influence decay rates, and synonymous codons with varying tRNA abundance affect translation efficiency and mRNA stability.
  • Ribosomal collisions from suboptimal codons can accelerate mRNA decay, and codon choice impacts amino acid misincorporation, potentially causing protein misfolding.

Purpose of the Study:

  • To investigate the effect of the aminoglycoside antibiotic Geneticin-G418 (G418), known to induce amino acid misincorporation, on mRNA stability.
  • To determine if G418 influences mRNA decay in both cell-free and cellular systems.

Main Methods:

  • Utilized an in vitro translation system to assess the impact of G418 on firefly luciferase mRNA stability.

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  • Evaluated G418's effect on mRNA stability in mouse embryonic stem cells (mESCs).
  • Analyzed G418-sensitive mRNAs for enrichment of specific codon types, particularly those with guanine (G) or cytosine (C) in the wobble position.

    • Main Results:

    • G418 was observed to decrease firefly luciferase mRNA stability in the in vitro translation system.
    • G418 treatment also led to reduced mRNA stability in mouse embryonic stem cells (mESCs).
    • mRNAs sensitive to G418 showed an enrichment of optimal codons containing G or C in the wobble position.

    Conclusions:

    • Geneticin-G418 reduces mRNA stability in both in vitro and cellular contexts.
    • The antibiotic appears to blunt the stabilizing influence of codon optimality, particularly for codons with G or C at the wobble position.
    • These findings highlight a mechanism where translation fidelity, influenced by antibiotics like G418, directly impacts mRNA decay rates and codon optimality effects.