Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

Jimena Giudice, Zheng Xia, Wei Li, Thomas A. Cooper

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number35550
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 19 2016
Externally publishedYes

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cdc Genes
RNA Stability
Transcriptome
Binding Sites
RNA Sequence Analysis
RNA-Binding Proteins
Ion Transport
Alternative Splicing
Protein Biosynthesis
Cytoplasm
Down-Regulation
Heart Failure
Gene Expression
Messenger RNA
Genes

ASJC Scopus subject areas

  • General

Cite this

Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1. / Giudice, Jimena; Xia, Zheng; Li, Wei; Cooper, Thomas A.

In: Scientific Reports, Vol. 6, 35550, 19.10.2016.

Research output: Contribution to journalArticle

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