Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulated local synthesis of ribosomal proteins maintains ribosome function in axons

ABSTRACT: Ribosome assembly occurs mainly in the nucleolus yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Here, we report a physical and functional interaction between locally synthesized RPs and ribosomes in the axon. We show that axonal RP translation is regulated through a novel sequence motif, CUIC, that forms an RNA-loop structure in the region immediately upstream of the initiation codon. Using imaging and subcellular proteomics techniques, we show that RPs synthesized in axons join axonal ribosomes in a nucleolus-independent fashion. Inhibition of axonal CUIC-regulated RP translation causes a significant decline in local translation activity and markedly reduces axon branching in the brain, revealing the physiological relevance of axonal RP synthesis in vivo. These results suggest that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus in neurons.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Xenopus Laevis (african Clawed Frog)

TISSUE(S): Brain, Retinal Ganglion Cell

SUBMITTER: Toshiaki Shigeoka

LAB HEAD: Christine E Holt

PROVIDER: PXD015574 | Pride | 2019-12-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

TMTpro16plex Isobaric Labeling Reagents: Attaining New Sample Multiplexing Heights and New Cellular Proteome Depths in Quantitative Proteomics

Project description:Isobaric labeling empowers proteome-wide expression measurements simultaneously across multiple samples. Here, an expanded set of 16 isobaric reagents based on a proline backbone (TMTpro) is presented. These reagents have similar characteristics to existing TMT reagents but with increased fragmentation efficiency and signal. In a proteome-scale example dataset, we compared eight common cell lines with and without Torin1 treatment with three replicates, quantifying more than 8,800 proteins (mean of 7.5 peptides/protein) per replicate with an analysis time of only 67 min per proteome examined. Finally, we modified the powerful thermal stability assay to examine proteome-wide melting shifts after treatment with DMSO, 1 or 20 µM staurosporine with five replicates. This new assay identified and dose-stratified the staurosporine binding to 228 cellular kinases in just one, 18-hr experiment. TMTpro reagents allow unprecedented complexity in experimental designs—all with basically no missing values across the 16 samples and no loss in quantitative integrity.

2020-03-19 | PXD014369 | Pride

TMTpro16plex Isobaric Labeling Reagents: Attaining New Sample Multiplexing Heights and New Cellular Proteome Depths in Quantitative Proteomics

Project description:Isobaric labeling empowers proteome-wide expression measurements simultaneously across multiple samples. Here, an expanded set of 16 isobaric reagents based on a proline backbone (TMTpro) is presented. These reagents have similar characteristics to existing TMT reagents but with increased fragmentation efficiency and signal. In a proteome-scale example dataset, we compared eight common cell lines with and without Torin1 treatment with three replicates, quantifying more than 8,800 proteins (mean of 7.5 peptides/protein) per replicate with an analysis time of only 67 min per proteome examined. Finally, we modified the powerful thermal stability assay to examine proteome-wide melting shifts after treatment with DMSO, 1 or 20 ��M staurosporine with five replicates. This new assay identified and dose-stratified the staurosporine binding to 228 cellular kinases in just one, 18-hr experiment. TMTpro reagents allow unprecedented complexity in experimental designs��all with basically no missing values across the 16 samples and no loss in quantitative integrity.

2020-03-19 | PXD016940 | Pride

TMTpro16plex Isobaric Labeling Reagents: Attaining New Sample Multiplexing Heights and New Cellular Proteome Depths in Quantitative Proteomics

2020-03-19 | PXD016491 | Pride

Mig6 mediates adaptive and acquired resistance to ALK and ROS1 fusion kinase inhibition through feedback activation of EGFR: H3122

Project description:ALK and ROS1 fusions defines subsets of lung adenocarcinoma. Although ALK/ROS1 inhibitors improved therapeutic outcome of patients harboring those oncogenic fusions, complete responses were rare, and resistance eventually develops from the residual tumor. To under the mechanisms contributing to residual tumor formation, we performed phosphoproteomics to explore the signaling adaption shortly after ALK/ROS1 inhibition. We found the phosphorylation of Mig6, a potent inhibitor for EGFR, was decreased following ALK/ROS1 inhibition, impairing Mig6 binding and inhibition on EGFR. Furthermore, Mig6 mRNA and protein levels were decreased rapidly by ALK/ROS1 inhibitors, potentiating EGFR activity to support cell survival. We also uncovered a novel mechanism mediated by Mig6 to regulate EGFR activity without impacting EGFR phosphorylation, but rather altering signaling adaptor SHC1 binding to EGFR. Mig6 expression was also lost following long-term exposure to ALK/ROS1 inhibitors to support EGFR-mediated acquired resistance. Finally, a Mig6 EGFR-binding domain truncation mutation was identified in a patient-derived ROS1 cell line, rendering its resistance to ROS1 inhibitors but sensitivity to HER family inhibitors. Our work established a rationale to evaluate combinations of ALK/ROS1 and EGFR inhibitors to limit residual tumor formation, therefore preventing or delaying subsequent resistance emergence.

2023-09-12 | PXD036772 | Pride

Mig6 mediates adaptive and acquired resistance to ALK and ROS1 fusion kinase inhibition through feedback activation of EGFR: Cuto28

2023-09-12 | PXD036771 | Pride

ChIP-seq for Hoxa2 on mouse second branchial arches at E11.5.

Project description:Hoxa2 ChIP-seq on mouse second branchial arch (BA2) at embryonic day (E) 11.5.

2020-01-06 | E-MTAB-7766 | biostudies-arrayexpress

Regulated local synthesis of ribosomal proteins maintains ribosome function in axons

Project description:Ribosome assembly occurs mainly in the nucleolus yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) in axons, far away from neuronal cell bodies. Here, we report a physical and functional interaction between locally synthesized RPs and ribosomes in the axon. We show that axonal RP translation is regulated through a novel sequence motif, CUIC, that forms an RNA-loop structure in the region immediately upstream of the initiation codon. Using imaging and subcellular proteomics techniques, we show that RPs synthesized in axons join axonal ribosomes in a nucleolus-independent fashion. Inhibition of axonal CUIC-regulated RP translation causes a significant decline in local translation activity and markedly reduces axon branching in the brain, revealing the physiological relevance of axonal RP synthesis in vivo. These results suggest that axonal translation supplies cytoplasmic RPs to maintain/modify local ribosomal function far from the nucleolus in neurons.

2019-12-11 | GSE135502 | GEO

Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells

Project description:FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-08 | PXD029981 | Pride

Proteogenomics of ex vivo-activated platelets.

Project description:Platelets are major players in the process of intravascular thrombus formation. Current therapeutic strategies still fail to prevent thrombotic coronary events in a substantial number of patients, indicating that the complex mechanisms modulating platelet response during activation are not fully elucidated. The evidence that platelets are capable of de novo protein synthesis has raised the issue of whether and how these resident mRNAs are regulated in circulating platelets. Among the several mechanisms potentially involved, mRNA splicing may be relevant. Purified platelet-rich plasmas from healthy volunteers were collected and in vitro activated with collagen or Thrombin Receptor Activating Peptide (TRAP). Transcriptome profiling by RNA-Seq and in silico intron representation analysis were applied to search for the presence of pre-mRNA molecules and splicing events affected by platelet activation. HiRIEF LC-MS allowed platelet proteome characterization at deep coverage to investigate a possible correlation between splicing events and protein levels. By comparing computational and wet-lab analyses it was possible to identify a set of transcripts influenced at both intron and protein level.

2018-01-03 | PXD006559 | Pride

ego3-Studying the transcriptional consequences of a QTL for shoot growth (SG3, SG1). Studying the transcriptional consequences of a QTL for shoot growth under mannitol condition (EGO3).

Project description:ra09-01_qtlleafgrowth - ego3 - What are the transcriptional consequences of the allelic contrast at SG3, SG1 and EGO3 loci mapped for its effect on shoot growth and identified at the gene level - Plants were grown in the in vitro conditions with 60 mM mannitol, where we have mapped and cloned the concerned QTL which allows us to see the phenotype linked to the segregation of the natural alleles. We are comparing 2 genotypes descending from a RIL from the Cvi x Col (H1 is Col allele containing HIF, and A2 is Cvi allele containing HIF). 2 dye-swap - genotype comparison

2012-04-06 | E-GEOD-36698 | 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