Ontology highlight
ABSTRACT:
PROVIDER: PRJNA854319 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19905808_1.fastq.gz | Fastqsanger.gz | |||
| SRR19905808_2.fastq.gz | Fastqsanger.gz | |||
| SRR19905809_1.fastq.gz | Fastqsanger.gz | |||
| SRR19905809_2.fastq.gz | Fastqsanger.gz | |||
| SRR19905810_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Context-dependent translation inhibition by the polyketide antibiotic Tetracenomycin X
| PRJNA838796 | ENA
Project description:Kasugamycin (KSG) is an aminoglycoside antibiotic widely used in agriculture and exhibiting considerable medical potential. Previous studies suggested that KSG interferes with translation by blocking binding of canonical mRNA and initiator 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. We also show that KSG inhibits protein synthesis in a gene- and context-specific manner as even saturating concentrations of KSG do not completely abolish translation of all Escherichia coli genes. 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 the first example of a small ribosomal subunit-targeting antibiotic with a well-pronounced context specificity of action.
2022-02-02 | GSE185757 | GEO
Project description:Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here we found that a broad range of ribosome-targeting antibiotics caused mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we found that the translation inhibitor caused genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis showed that the stalling was caused by disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induced lesions to the DNA via transcription-coupled repair. While most of the bacteria were killed by genotoxicity, a small subpopulation acquired mutations via SOS-induced mutagenesis. Given that these processes were triggered shortly after antibiotic addition, resistance rapidly emerged in the population. Our work revealed a new mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance.
2024-05-15 | GSE267245 | GEO
Project description:Context-specific inhibition of translation by ribosomal antibiotics targeting the peptidyl transferase center
| PRJNA342154 | ENA
Project description:Chromatin remodeling and protein synthesis are tightly regulated processes that impact gene expression and cellular phenotypes. However, it is unknown if these two regulatory mechanisms are linked or exert independent effects in normal epithelial physiology and disease states. We have uncovered a new functional relationship between the chromatin remodeler ARID1A and mRNA translation elongation that is involved in maintaining cellular fitness in the context of bladder carcinogenesis. Loss of ARID1A triggers inhibition of the translation elongation factor eEF2 and ribosome accumulation, which results in a reduction in protein synthesis. In the setting of ARID1A deficiency the bladder carcinogen BBN induces DNA damage and cell death without impacting cancer initiation. As such, ARID1A is necessary for tumorigenesis. Remarkably, restoration of translation elongation through eEF2 is sufficient to initiate transformation in the context of ARID1A loss. However, dependence on ARID1A for transformation appears to be context specific, as loss of ARID1A after tumor establishment is sufficient for cancer progression.
2023-03-13 | GSE201220 | GEO
Project description:Bacteria often evolve antibiotic resistance through mutagenesis. However, the processes causing the mutagenesis have not been fully resolved. Here we found that a broad range of ribosome-targeting antibiotics caused mutations through an underexplored pathway. Focusing on the clinically important aminoglycoside gentamicin, we found that the translation inhibitor caused genome-wide premature stalling of RNA polymerase (RNAP) in a loci-dependent manner. Further analysis showed that the stalling was caused by disruption of transcription-translation coupling. Anti-intuitively, the stalled RNAPs subsequently induced lesions to the DNA via transcription-coupled repair. While most of the bacteria were killed by genotoxicity, a small subpopulation acquired mutations via SOS-induced mutagenesis. Given that these processes were triggered shortly after antibiotic addition, resistance rapidly emerged in the population. Our work revealed a new mechanism of action of ribosomal antibiotics, illustrates the importance of dissecting the complex interplay between multiple molecular processes in understanding antibiotic efficacy, and suggests new strategies for countering the development of resistance.
2024-06-24 | GSE240474 | GEO
Project description:Gene expression is a dynamic process regulated on several layers starting with transcription, mRNA export, translation and finally, mRNA degradation. While subsequent layers heavily influence each other, it is not clear if the most extreme layers, chromatin architecture and mRNA decay are linked. Here, we show that changes in nascent transcription mediated by mutating H3K56 to alanine are buffered at a post-transcriptional level by the Pumilio protein Puf5, which stabilizes transcripts in a context-dependent manner. Depleting Puf5 in an H3K56A background leads to downregulation of its direct targets, largely consisting of ribosomal protein genes. This is followed by a decrease in translation efficiency and finally, cell cycle arrest. Importantly, we show that this phenomenon of post-transcriptional buffering is not only linked to H3K56A, but might be a more widespread phenomenon to ensure physiological mRNA levels and to maintain cellular homeostasis.
2021-07-19 | E-MTAB-10105 | biostudies-arrayexpress
Project description:The control of mRNA stability plays a central role in regulating gene expression. In metazoans, the earliest stages of development are driven by maternally supplied mRNAs. The degradation of these maternal mRNAs is critical for promoting the maternal-to-zygotic transition of developmental programs, although the underlying mechanisms are poorly understood in vertebrates. Here, we characterized maternal mRNA degradation pathways in zebrafish using a transcriptome analysis and systematic reporter assays. Our data demonstrate that ORFs enriched with uncommon codons promote deadenylation by the CCR4-NOT complex in a translation-dependent manner. This codon-mediated mRNA decay is conditional on the context of the 3â² UTR, with long 3â² UTRs conferring resistance to deadenylation. These results indicate that the combined effect of codon usage and 3â² UTR length determines the stability of maternal mRNAs in zebrafish embryos. Our study thus highlights the codon-mediated mRNA decay as a conserved regulatory mechanism in eukaryotes. zebrafish embryonic mRNA profile at 2 different stages (2 hpf and 6 hpf) in wildtype and 3 additional conditions (miR-430 inhibition, RNApol II inhibition and CNOT7 inhibition) at 6 hpf. All experiments are performed as triplicates
2016-03-17 | E-GEOD-71609 | biostudies-arrayexpress
Project description:Abstract: Transcript levels in production cultures of wildtype and classically improved strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces fradiae were monitored using microarrays of the sequenced actinomycete S. coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics erythromycin and tylosin, respectively, and the classically improved strains contain unknown overproduction mutations. The Sac. erythraea overproducer was found to express the entire 56-kb erythromycin gene cluster several days longer than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while they expressed several tens of other S. fradiae genes and S. coelicolor homologs differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor isobutyryl-CoA mutase homolog icmA. These observations indicated that overproduction mechanisms in classically improved strains can affect both the timing and rate of antibiotic synthesis, and alter the regulation of antibiotic biosynthetic enzymes and enzymes involved in precursor metabolism. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2006-03-08 | E-GEOD-4395 | biostudies-arrayexpress