Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cellular response to small molecules that selectively stall protein synthesis by the ribosome

ABSTRACT: We use ribosome profiling to compare the selectivity of two small molecules, PF-06446846 and PF-06378503 that inhibits translation of their target by selectively inducing ribosome-stalling in a nascent chain sequence dependent manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE121981 | GEO | 2019/03/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Selective stalling of human translation through small molecule engagement of the ribosome nascent chain

Project description:We use ribosome profiling to demonstrate the selectivity of a small molecule, PF-06446846 that inhibits translation of its target by selectively inducing ribosome-stalling in a nascent chain sequence dependent manner.

2017-06-05 | GSE94454 | GEO

SECRETOME DATA only from “Selective stalling of human translation through small molecule engagement of the ribosome nascent chain”

Project description:Human genetics as well as pharmacological intervention reveal that Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a key role in regulating the levels of plasma low density lipoprotein cholesterol (LDL-C). Here we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by stalling the ribosome near codon 34 of its messenger RNA. Inhibition by PF-06446846 is sensitive to the amino acid sequence of the PCSK9 nascent chain, and not the messenger RNA. PF-06446846 also reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling to examine the proteome-wide effects of PF-06446846, we find that it is exceptionally specific for PCSK9 and has no measurable effect on 99.7% of the translatome at concentrations sufficient for 90% inhibition of PCSK9 expression. Together, PF-06446846 represents the first example of an orally administered small molecule directly targeting PCSK9 that functions by a mechanism inhibiting translation during elongation with a high degree of selectivity. Selective inhibition of translation in human may represent a new approach to target proteins with small molecules.

2017-03-27 | PXD005822 | Pride

CELL LYSATE DATA only from “Selective stalling of human translation through small molecule engagement of the ribosome nascent chain”

2017-03-27 | PXD005835 | Pride

Cellular response to small molecules that selectively stall protein synthesis by the ribosome.

Project description: Not available

| S-EPMC6436758 | biostudies-literature

Cellular response to small molecules that selectively stall protein synthesis by the ribosome

Project description:Cellular response to small molecules that selectively stall protein synthesis by the ribosome

| PRJNA501880 | ENA

Bacterial ribosome pause sites surveyed by an integration of ribosome profiling and nascent chain profiling

Project description:Ribosome pauses are associated with diverse co-translational events and determine the fate of mRNAs and proteins. Thus the identification of the precise pause sites across transcriptome is a key, however, the landscape in bacterial has remained ambiguous. Here, we harnessed the multiple ribosome profiling strategies (standard, high-salt-wash, and disome) to survey the robust ribosome pause sites in E. coli. The found pause sites showed the correspondence with biochemical validation by integrated nascent chain profiling (iNP), which detects polypeptidyl-tRNA, an elongation intermediate. Among the list, ribosome pause at Asn586 of ycbZ was ensured by biochemical reporter assay, tRNA-seq, and cryo-electron microscopy. Our results provide a useful resource of ribosome stalling sites in bacteria.

2021-11-23 | GSE160623 | GEO

Small Molecule PCSK9 Inhibitors: Hit to lead optimization

Project description:Ribosome profiling is used to demonstrate improved selectivity of compounds that promote PCSK9 translational stalling

2018-06-20 | GSE110426 | GEO

Bacterial ribosome pause sites surveyed by an integration of ribosome profiling and nascent chain profiling II

2021-11-23 | GSE180482 | GEO

Project description:Nascent chain libraries probing PF-06446846-dependent stalling

| PRJNA533782 | ENA

Translational control through ribosome traffic jams and aborted protein synthesis

Project description:Translational control is a widespread mode of gene regulation in organisms ranging from bacteria to mammals. Computational models posit that translational control of protein expression during elongation is exerted through a traffic jam of multiple ribosomes at ribosome pause sites on mRNAs. Yet neither the in vivo frequency of ribosome traffic jams nor the contribution of such traffic jams to protein expression has been measured in any organism. Here we show that upon starvation for single amino acids in the bacterium Escherichia coli, ribosome traffic jams are pervasive across the transcriptome, but they occur at only a subset of codons cognate to the limiting amino acid, and their severity is determined by the translation efficiency of mRNAs. Surprisingly, a computational model based on the observed traffic jams at ribosome pause sites is quantitatively inconsistent with measured protein synthesis rates. By comparison, a model incorporating abortion of protein synthesis at ribosome pause sites in addition to ribosome traffic jams predicts protein synthesis rate with higher accuracy. Consistent with the latter model, a significant fraction of the nascent polypeptides at ribosome pause sites is degraded through the activity of the transfer-messenger RNA during amino acid starvation in E. coli. Our work provides a minimal, experimentally-constrained model for predicting protein expression from ribosome dynamics, and it suggests the existence of a trade-off between the cellular translational capacity and the processivity of protein synthesis in vivo. 6 samples for ribosome profiling and 5 samples for total mRNA profiling

2014-05-15 | E-GEOD-51052 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data