Doroudgar et al. 2019 (PRJNA484227)

General Details

Title Monitoring translational control by Ribo-seq during pressure overload in vivo using a genetic intersectional technology called Ribo-tag at different timepoints
Organism
Number of Samples 32
Release Date 2018/08/02 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP156230
ENA SRP156230
GEO 0.0
BioProject PRJNA484227

Publication

Title
Authors Doroudgar S, Hofmann C, Boileau E, Malone B, Riechert E, Gorska AA, Jakobi T, Sandmann C, Jürgensen L, Kmietczyk V, Malovrh E, Burghaus J, Rettel M, Stein F, Younesi F, Friedrich UA, Mauz V, Backs J, Kramer G, Katus HA, Dieterich C, Völkers M
Journal Circulation research
Publication Date 2019 Aug 2
Abstract Gene expression profiles have been mainly determined by analysis of transcript abundance. However, these analyses cannot capture posttranscriptional gene expression control at the level of translation, which is a key step in the regulation of gene expression, as evidenced by the fact that transcript levels often poorly correlate with protein levels. Furthermore, genome-wide transcript profiling of distinct cell types is challenging due to the fact that lysates from tissues always represent a mixture of cells. This study aimed to develop a new experimental method that overcomes both limitations and to apply this method to perform a genome-wide analysis of gene expression on the translational level in response to pressure overload. By combining ribosome profiling (Ribo-seq) with a ribosome-tagging approach (Ribo-tag), it was possible to determine the translated transcriptome in specific cell types from the heart. After pressure overload, we monitored the cardiac myocyte translatome by purifying tagged cardiac myocyte ribosomes from cardiac lysates and subjecting the ribosome-protected mRNA fragments to deep sequencing. We identified subsets of mRNAs that are regulated at the translational level and found that translational control determines early changes in gene expression in response to cardiac stress in cardiac myocytes. Translationally controlled transcripts are associated with specific biological processes related to translation, protein quality control, and metabolism. Mechanistically, Ribo-seq allowed for the identification of upstream open reading frames in transcripts, which we predict to be important regulators of translation. This method has the potential to (1) provide a new tool for studying cell-specific gene expression at the level of translation in tissues, (2) reveal new therapeutic targets to prevent cellular remodeling, and (3) trigger follow-up studies that address both, the molecular mechanisms involved in the posttranscriptional control of gene expression in cardiac cells, and the protective functions of proteins expressed in response to cellular stress.
PMC PMC6690133
PMID 31284834
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR7640021 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640019 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640017 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640015 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640013 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640011 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640009 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640007 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640005 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640003 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7640002 PRJNA484227 Rattus norvegicus 0.0 Ribo-Seq 0.0
SRR7640000 PRJNA484227 Rattus norvegicus 0.0 Ribo-Seq 0.0
SRR7639998 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR7639996 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874836 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874835 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874834 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874833 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874832 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874828 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874825 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874824 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874822 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874820 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874819 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874818 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874817 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874815 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874813 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874807 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874806 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
SRR8874802 PRJNA484227 Mus musculus 0.0 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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