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Title: Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1      
keywords:
Transcriptome or Gene expression
ID:
PRJNA338992
description:
The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated. Overall design: RNA-seq was performed in RNA samples of cardiac ventricles at postnatal day 3 (PN3) and at postnatal day 38 (PN38) from wild type mice or Celf1 knock out mice (homozygous)
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA338992
authentication:
none
authorization:
none
ID:
pmid:27759042
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R01 CA193466/CA/NCI NIH HHS/United States

  • R01 AR045653/AR/NIAMS NIH HHS/United States

  • R01 AR060733/AR/NIAMS NIH HHS/United States

  • U54 HG006348/HG/NHGRI NIH HHS/United States

  • R01 HG007538/HG/NHGRI NIH HHS/United States

  • R01 HL045565/HL/NHLBI NIH HHS/United States

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