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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts

Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts

Published on: January 2, 2018

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.

|July 28, 2022

Summary

This summary is machine-generated.

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.

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Published on: December 13, 2014

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.
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.