Zhang et al. 2022 (PRJNA770675)

General Details

Title The context of the ribosome binding site in mRNAs defines specificity of action of kasugamycin, an inhibitor of translation initiation
Organism
Number of Samples 3
Release Date 2021/10/12 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP341055
ENA SRP341055
GEO GSE185757
BioProject PRJNA770675

Publication

Title
Authors Zhang Y, Aleksashin NA, Klepacki D, Anderson C, Vázquez-Laslop N, Gross CA, Mankin AS
Journal Proceedings of the National Academy of Sciences of the United States of America
Publication Date 2022 Jan 25
Abstract Kasugamycin (KSG) is an aminoglycoside antibiotic widely used in agriculture and exhibits considerable medical potential. Previous studies suggested that KSG interferes with translation by blocking binding of canonical messenger RNA (mRNA) and initiator transfer tRNA (tRNA) to the small ribosomal subunit, thereby preventing initiation of protein synthesis. Here, by using genome-wide approaches, we show that KSG can interfere with translation even after the formation of the 70S initiation complex on mRNA, as the extent of KSG-mediated translation inhibition correlates with increased occupancy of start codons by 70S ribosomes. Even at saturating concentrations, KSG does not completely abolish translation, allowing for continuing expression of some Escherichia coli proteins. Differential action of KSG significantly depends on the nature of the mRNA residue immediately preceding the start codon, with guanine in this position being the most conducive to inhibition by the drug. In addition, the activity of KSG is attenuated by translational coupling as genes whose start codons overlap with the coding regions or the stop codons of the upstream cistrons tend to be less susceptible to drug-mediated inhibition. Altogether, our findings reveal KSG as an example of a small ribosomal subunit-targeting antibiotic with a well-pronounced context specificity of action. Copyright © 2022 the Author(s). Published by PNAS.
PMC PMC8794815
PMID 35064089
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR16301571 PRJNA770675 Escherichia coli 0.0 Ribo-Seq 0.0
SRR16301572 PRJNA770675 Escherichia coli 0.0 Ribo-Seq 0.0
SRR16301570 PRJNA770675 Escherichia coli 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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