Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Eukaryotic translation initiation factor 2A protects pancreatic beta cells during endoplasmic reticulum stress while rescuing translation inhibition

ABSTRACT: Eukaryotic translation initiation factor 2A protects pancreatic beta cells during endoplasmic reticulum stress while rescuing translation inhibition

PROVIDER: PRJNA702091 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13720900_1.fastq.gz	Fastqsanger.gz
	SRR13720900_2.fastq.gz	Fastqsanger.gz
	SRR13720901_1.fastq.gz	Fastqsanger.gz
	SRR13720901_2.fastq.gz	Fastqsanger.gz
	SRR13720902_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 192

Similar Datasets

Eukaryotic translation initiation factor 2A protects pancreatic beta cells during endoplasmic reticulum stress while rescuing translation inhibition

Project description:Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) helps decide b cell survival in diabetes. The alternative eukaryotic initiation factor 2A (EIF2A) has been proposed to mediate EIF2S1-independent translation during cellular stress and viral infection, but its role in b cells is unknown. EIF2A abundance is high in human and mouse islets relative to other tissues, and both thapsigargin and palmitate significantly increased EIF2A mRNA and EIF2A protein levels in MIN6 cells, mouse islets and human islets. Knockdowns of EIF2A, the related factor EIF2D, or both EIF2A and EIF2D, were not sufficient to cause apoptosis. On the other hand, transient or stable EIF2A over-expression protected MIN6 cells, primary mouse islets, and human islets from ER stress-induced, caspase-3-dependent apoptosis. Mechanistically, EIF2A overexpression decreased ERN1 (also known as IRE1a) expression in thapsigargin-treated MIN6 cells or human islets. In vivo, b cell specific EIF2A viral overexpression reduced ER stress, improved insulin signaling, and abrogated hyperglycemia in Ins2Akita/WT mice. EIF2A overexpression significantly increased expression of genes involved protein translation and reduced expression of pro-apoptotic genes (e.g. ALDH1A3). Remarkably, the decrease in global protein synthesis during UPR was prevented by EIF2A, despite ER stress-induced EIF2S1 phosphorylation. The protective effects of EIF2A were additive to those of ISRIB, a drug that counteracts the effects of EIF2S1 phosphorylation. Cells overexpressing EIF2A showed higher expression of translation factor EIF2B5, which may contribute to the lack of translational inhibition in these cells. We conclude that EIF2A is a novel target for b cell protection and the circumvention of EIF2S1-mediated translational repression.

2022-08-31 | GSE166829 | GEO

Ribosome footprinting in the cytosol and endoplasmic reticulum

Project description:In eukaryotic cells, the spatial regulation of protein expression is frequently conferred through the coupling of mRNA localization and the local control of translation. mRNA localization to the endoplasmic reticulum (ER) is a prominent example of such regulation and serves a ubiquitous role in segregating the synthesis of secretory and integral membrane proteins to the ER. Recent genomic and biochemical studies have now expanded this view to suggest a role for the ER in global protein synthesis. We have utilized cell fractionation and ribosome profiling to obtain a genomic survey of the subcellular organization of mRNA translation and report that ribosomal loading of mRNAs, a proxy for mRNA translation, is biased to the ER. Notably, ER-associated mRNAs encoding both cytosolic and topogenic signal-encoding proteins display similar ribosome loading densities, suggesting that ER-associated ribosomes serve a global role in mRNA translation. We propose that the partitioning of mRNAs and their translation between the cytosol and ER compartments may represent a novel mechanism for the post-transcriptional regulation of gene expression. HEK293 cells were fractionated between the cytosol and endoplasmic reticulum. Within each fraction, ribosome footprints were generated and sequenced. In parallel, total mRNA was sequenced.

2011-12-20 | E-GEOD-31539 | biostudies-arrayexpress

Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (HDLBP PAR-CLIP)

Project description:Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (HDLBP PAR-CLIP)

| PRJNA623611 | ENA

Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (tRNA ncRNA-seq)

Project description:Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (tRNA ncRNA-seq)

| PRJNA623615 | ENA

Reduced a-MSH underlies hypothalamic endoplasmic reticulum stress-induced hepatic gluconeogenesis

Project description:Alterations in endoplasmic reticulum (ER) homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (a-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic a-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective a-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress, and establish a-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Total RNA was extracted from whole-liver of 6-week old control (3 biological replicates) and POMCMfn2KO mice (5 biological replicates)

2015-06-18 | E-GEOD-62263 | biostudies-arrayexpress

Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (Cell fractionation RNA-seq)

Project description:Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (Cell fractionation RNA-seq)

| PRJNA623610 | ENA

Meta-organization of Translation Centers Revealed by Proximity Mapping of Endoplasmic Reticulum Ribosome Interactors

Project description:We report a method to use BioID proximity labeling to map the sub-organization of translating mRNAs on the endoplasmic reticulum. This method first isolates membrane bound polysomes using a Sephacryl 400 resin-based enrichment followed by isolation of biotin labeled polysomes by streptavidin beads and high-throughput sequencing of the bound polysomes. We find that, for the two pools of polysomes labeled by either LRRC59 or Sec61beta BioID reporters, there is an interesting divergence in specific mRNAs that are entering into the secretory pathway such that secreted proteins are much more enriched towards the LRRC59 reporter with Sec61beta serving a more varied role in mRNA translation.

2019-04-18 | GSE118873 | GEO

Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (A549 HDLBP KO and WT)

Project description:Vigilin/HDLBP promotes translation of endoplasmic reticulum-targeted mRNAs (A549 HDLBP KO and WT)

| PRJNA633162 | ENA

Meta-organization of Translation Centers Revealed by Proximity Mapping of Endoplasmic Reticulum Ribosome Interactors

Project description:Meta-organization of Translation Centers Revealed by Proximity Mapping of Endoplasmic Reticulum Ribosome Interactors

| PRJNA487078 | ENA

Alternative 3’UTRs play a widespread role in translation-independent mRNA association with endoplasmic reticulum

Project description:Transcripts encoding membrane and secreted proteins are known to undergo translation on endoplasmic reticulum (ER). Translation-independent ER association (TiERA) has been reported for certain mRNAs, but the phenomenon is poorly understood. Here, using cell fractionation, polysome profiling, and 3’ end sequencing, we examine TiERA of poly(A)+ RNAs in mouse C2C12 myoblast cells. We identify transcript features that facilitate TiERA, including transcript size and GG and GC content. Consistent with the feature analysis, alternative polyadenylation (APA) isoforms differ substantially in TiERA, with long 3’UTR isoforms generally having a higher TiERA potential than short 3’UTR isoforms. Importantly, the widespread 3’UTR lengthening taking place in cell differentiation leads to greater transcript association with ER in differentiated myotubes, despite that the TiERA potential being generally maintained. In addition, we show that TiERA correlates negatively with mRNA stability, highlighting 3’UTR-mediated mRNA decay on ER. Together, our data indicate that sequence and size features impact ER association independent of translation, leading to distinct mRNA metabolism for different transcript groups, and APA can alter transcript stability and translation through isoform-specific ER association.

2021-07-20 | GSE162971 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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