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Title:
Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes | Genome Biology
Description:
Background Oxygen and glucose metabolism play pivotal roles in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) during ischemia and stroke results in extensive tissue injury and cell death. Results Using time-resolved ribosome profiling, we assess gene expression levels in a neural cell line, PC12, during the first hour of OGD. The most substantial alterations are seen to occur within the first 20 minutes of OGD. While transcription of only 100 genes is significantly altered during one hour of OGD, the translation response affects approximately 3,000 genes. This response involves reprogramming of initiation and elongation rates, as well as the stringency of start codon recognition. Genes involved in oxidative phosphorylation are most affected. Detailed analysis of ribosome profiles reveals salient alterations of ribosome densities on individual mRNAs. The mRNA-specific alterations include increased translation of upstream open reading frames, site-specific ribosome pauses, and production of alternative protein isoforms with amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals six mRNAs with translated ORFs occurring downstream of annotated coding regions and two examples of dual coding mRNAs, where two protein products are translated from the same long segment of mRNA, but in two different frames. Conclusions These findings uncover novel regulatory mechanisms of translational response to OGD in mammalian cells that are different from the classical pathways such as hypoxia inducible factor (HIF) signaling, while also revealing sophisticated organization of protein coding information in certain genes.
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Keywords {🔍}
translation, pubmed, figure, article, ribosome, google, scholar, genes, ogd, cas, gene, mrnas, reads, analysis, response, additional, density, riboseq, mrna, file, central, expression, acorf, oxygen, number, protein, cells, conditions, codon, minutes, cell, initiation, profiles, deprivation, uorfs, glucose, elongation, increased, hypoxia, observed, stress, termination, data, levels, phosphorylation, profile, translational, profiling, translated, downstream,
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int/mediacentre/factsheets/fs310/en/ amp-activated protein kinase gov/refseq/r_norvegicus/mrna_prot/ aug-initiated n-terminal extensions numerous ogd-induced pauses article download pdf calculate local z-score pre-mixed kit reagents par-clip reads supporting full size image pre-made acrylamide gels pre-stained protein ladder celltiter-glo® atp assay site-specific ribosome pauses ogd-induced pause occurring high-throughput sequencing reads jc-1 forms j-aggregates time-resolved ribosome profiling mrna-seq cdna libraries ribo-seq occupancy alteration increasingly complex biology ribo-seq reads aligning aug-initiated overlapping orf ribosome-protected mrna fragments ribo-seq read density ribo-seq signal normalized acorf ribo-seq profiles ogd-induced uorf translation affects gene expression ribo-seq read mapped canonical hif-mediated response glucose deprivation alters related subjects mapped ribo-seq reads aligned ribo-seq reads ribo-seq read alignment short dna sequences hif-promoted transcriptional response hif-1α levels increase privacy choices/manage cookies early ogd-mediated reprogramming genome-wide gene ontology terms revealing sophisticated organization chemotherapy-induced apoptosis neural cell line gene expression precedes gene expression exhibited unfolded protein response celltiter-glo® assay
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headline:Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes
description:Oxygen and glucose metabolism play pivotal roles in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) during ischemia and stroke results in extensive tissue injury and cell death. Using time-resolved ribosome profiling, we assess gene expression levels in a neural cell line, PC12, during the first hour of OGD. The most substantial alterations are seen to occur within the first 20 minutes of OGD. While transcription of only 100 genes is significantly altered during one hour of OGD, the translation response affects approximately 3,000 genes. This response involves reprogramming of initiation and elongation rates, as well as the stringency of start codon recognition. Genes involved in oxidative phosphorylation are most affected. Detailed analysis of ribosome profiles reveals salient alterations of ribosome densities on individual mRNAs. The mRNA-specific alterations include increased translation of upstream open reading frames, site-specific ribosome pauses, and production of alternative protein isoforms with amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals six mRNAs with translated ORFs occurring downstream of annotated coding regions and two examples of dual coding mRNAs, where two protein products are translated from the same long segment of mRNA, but in two different frames. These findings uncover novel regulatory mechanisms of translational response to OGD in mammalian cells that are different from the classical pathways such as hypoxia inducible factor (HIF) signaling, while also revealing sophisticated organization of protein coding information in certain genes.
datePublished:2015-05-06T00:00:00Z
dateModified:2015-05-06T00:00:00Z
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PC12 Cell
Differentially Express
Differentially Express Gene
Glucose Deprivation
Translation Termination
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:Oxygen and glucose deprivation induces widespread alterations in mRNA translation within 20 minutes
description:Oxygen and glucose metabolism play pivotal roles in many (patho)physiological conditions. In particular, oxygen and glucose deprivation (OGD) during ischemia and stroke results in extensive tissue injury and cell death. Using time-resolved ribosome profiling, we assess gene expression levels in a neural cell line, PC12, during the first hour of OGD. The most substantial alterations are seen to occur within the first 20 minutes of OGD. While transcription of only 100 genes is significantly altered during one hour of OGD, the translation response affects approximately 3,000 genes. This response involves reprogramming of initiation and elongation rates, as well as the stringency of start codon recognition. Genes involved in oxidative phosphorylation are most affected. Detailed analysis of ribosome profiles reveals salient alterations of ribosome densities on individual mRNAs. The mRNA-specific alterations include increased translation of upstream open reading frames, site-specific ribosome pauses, and production of alternative protein isoforms with amino-terminal extensions. Detailed analysis of ribosomal profiles also reveals six mRNAs with translated ORFs occurring downstream of annotated coding regions and two examples of dual coding mRNAs, where two protein products are translated from the same long segment of mRNA, but in two different frames. These findings uncover novel regulatory mechanisms of translational response to OGD in mammalian cells that are different from the classical pathways such as hypoxia inducible factor (HIF) signaling, while also revealing sophisticated organization of protein coding information in certain genes.
datePublished:2015-05-06T00:00:00Z
dateModified:2015-05-06T00:00:00Z
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PC12 Cell
Differentially Express
Differentially Express Gene
Glucose Deprivation
Translation Termination
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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