Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DENR-regulated reinitiation events uncover predictive uORF features and links to circadian timekeeping via Clock regulation

ABSTRACT: DENR-regulated reinitiation events uncover predictive uORF features and links to circadian timekeeping via Clock regulation

PROVIDER: PRJNA513490 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

Project description:The non-canonical initiation factor DENR promotes translation reinitiation on uORF-containing mRNAs. Moreover, DENR depletion shortens circadian period in mouse fibroblasts, suggesting that uORF usage and reinitiation regulate clock function. To identify DENR-regulated translation events transcriptome-wide and, in particular, specific core clock transcripts affected by this mechanism, we have used ribosome profiling in DENR-deficient NIH3T3 cells. We found 240 transcripts with altered translation rate, and used linear regression analysis to extract uORF features predictive of DENR dependance. Among core clock genes, we identified Clock as a DENR target. Using Clock 5'UTR mutants, we mapped the specific uORF through which DENR acts to regulate CLOCK protein biosynthesis. Notably, these experiments identified an alternative downstream start codon, which likely represents the true CLOCK N-terminus. Our findings provide insights into uORF-mediated translational regulation that can regulate the mammalian circadian clock and gene expression at large.

2019-04-01 | GSE116221 | GEO

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

2019-04-01 | GSE124790 | GEO

Master stress response gene ATF4 & other oncogenes are translated by DENR-dependent reinitiation

Project description:Translation efficiency varies 1000-fold between different mRNAs, thereby strongly impacting protein expression. Translation of the master stress response gene ATF4 increases in response to stress, but the molecular mechanisms are not well understood. We discover here that translation initiation factors DENR, MCTS1 and eIF2D are absolutely required to induce ATF4 translation upon stress, by promoting translation reinitiation on the ATF4 5’UTR. Hence DENR and MCTS1 are important players in the cellular Integrated Stress Response. We find DENR and MCTS1 promote reinitiation after long uORFs with specific penultimate codons, due to the tRNA that remains attached to 40S ribosomes after translation termination. This provides a model for how DENR and MCTS1 promote translation reinitiation. Since cancer cells are exposed to many stresses, they require ATF4 for survival and proliferation. We find a strong correlation between DENR•MCTS1 expression and ATF4 activity across cancers. Additional oncogenes including a-Raf, c-Raf and Cdk4 have long uORFs and are translated in a DENR•MCTS1 dependent manner. This explains in part why DENR and MCTS1 are oncogenes.

2020-07-18 | GSE140084 | GEO

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

Project description:Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

| PRJNA513492 | ENA

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

Project description:Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock

| PRJNA477799 | ENA

DENR-regulated reinitiation events uncover predictive uORF features and links to circadian timekeeping via Clock regulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-04-01 | GSE124793 | GEO

Charting DENR-dependent translation reinitiation uncovers predictive uORF features and links to circadian timekeeping via Clock.

Project description: Not available

| S-EPMC6547434 | biostudies-literature

Polysomes from DENR knockdown cells

Project description:The aim was to identify transcripts that are poorly translated upon knockdown of DENR. Lysates from control (GFP) and DENR knockdown S2 cells were run on polysome gradients. RNA from the (80S peak + polysome peaks) was isolated and analyzed by microarrays. In parallel, total RNA from the cells was also profiled as a normalization control and profiled. The 'translation score' of translated mRNA to total RNA was then calculated for control and DENR knockdown cells. Two biological replicates for DENR knockdown and GFP knockdown were performed. For each sample, (80S+polysomes) and total RNA were profiled, leading to 8 samples in total.

2014-06-30 | E-GEOD-54625 | biostudies-arrayexpress

Master stress response gene ATF4 & other oncogenes are translated by DENR-dependent reinitiation

Project description:Master stress response gene ATF4 & other oncogenes are translated by DENR-dependent reinitiation

| PRJNA588223 | ENA

Dynamic O-GlcNAcylation of eIF3a controls translation reinitiation during integrated stress response

Project description:In eukaryotic cells, many mRNAs possess upstream open reading frames (uORFs) in addition to the main coding region. After uORF translation, the ribosome could either recycle at the stop codon or resume scanning for downstream start codons in a process known as reinitiation. Accumulating evidence suggests that some initiation factors, including eIF3, linger on the early elongating ribosome, forming an eIF3-80S complex. Very little is known how the eIF3 is carried along with the 80S during elongation and its implications in subsequent translation reinitiation. Here we report that eIF3a undergoes dynamic O-GlcNAc modification in response to nutrient starvation. Stress-induced de-O-GlcNAcylation promotes eIF3 retention on the elongating ribosome and facilitates reinitiation at downstream start codons. Eliminating the modification site from eIF3a via genome editing induces ATF4 reinitiation under the nutrient rich condition. Our findings illustrate a mechanism in balancing ribosome recycling and reinitiation, thereby linking integrated stress response and translational reprogramming.

2021-11-01 | GSE181040 | GEO

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