title: Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1.
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.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, NC, 27599, USA.
authors.forename: Jimena
authors.initials: J
authors.lastname: Giudice
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.|Division of Biostatistics, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.|Division of Biostatistics, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.|Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Cooper
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D000067879:CELF1 Protein / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000254:growth & development* / Q000502:physiology; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000235:genetics; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D059467:Transcriptome
chemical_list: D000067879:CELF1 Protein; D012333:RNA, Messenger