@article{613844cb40ec4c21aad38c546e5b518f,
title = "Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development",
abstract = "During postnatal development the heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). Here we perform deep RNA-sequencing on RNA from cardiomyocytes and cardiac fibroblasts to conduct a high-resolution analysis of transcriptome changes during postnatal mouse heart development. We reveal extensive changes in gene expression and AS that occur primarily between postnatal days 1 and 28. Cardiomyocytes and cardiac fibroblasts show reciprocal regulation of gene expression reflecting differences in proliferative capacity, cell adhesion functions and mitochondrial metabolism. We further demonstrate that AS plays a role in vesicular trafficking and membrane organization. These AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated changes in expression. Vesicular trafficking genes affected by AS during normal development (when Celf1 is downregulated) show a reversion to neonatal splicing patterns after Celf1 re-expression in adults. Short-term Celf1 induction in adult animals results in disrupted transverse tubule organization and calcium handling. These results identify potential roles for AS in multiple aspects of postnatal heart maturation, including vesicular trafficking and intracellular membrane dynamics.",
author = "Jimena Giudice and Zheng Xia and Wang, {Eric T.} and Scavuzzo, {Marissa A.} and Ward, {Amanda J.} and Auinash Kalsotra and Wei Wang and Wehrens, {Xander H.T.} and Burge, {Christopher B.} and Wei Li and Cooper, {Thomas A.}",
note = "Funding Information: We thank Donnie Bundman (Baylor College of Medicine) for technical assistance, Rebecca L. Thornton (Baylor College of Medicine) for help with RNA-seq details, Corey L. Reynolds and Mouse Phenotyping Core (Baylor College of Medicine) for electro-and echocardiograms, Gloria Vittone-Echeverria, Simona Pedrotti and Ravi Singh (Baylor College of Medicine) for critical reading of the manuscript. This project was funded by the NIH (R01HL045565, R01AR060733 and R01AR045653) and Muscular Dystrophy Association (MDA 276796) grants to T.A.C. RNA-seq was performed in the Genomic and RNA Profiling Core (Baylor College of Medicine) with the assistance of the Core Director (L.D. White, PhD). J.G. is a Pew Latin American Fellow in the Biomedical Sciences supported by The Pew Charitable Trusts (#2933). E.T.W. was funded by a post-doctoral fellowship from Myotonic Dystrophy Foundation. A.K. is funded by the American Heart Association (scientist development Grant-11SDG4980011). A.J.W. was funded by National Institute of Neurological Disorders and Stroke (NINDS-F31NS067740). W.L. is funded by CPRIT (RP110471), DOD (W81XWH-10-1-0501) and NIH (R01HG007538) grants. X.H.T.W. is funded by NIH (HL089598, HL091947 and HL117641), the American Heart Association (13EIA14560061), Muscular Dystrophy Association (186530) and Fondation Leducq (08CVD01) grants.",
year = "2014",
month = apr,
day = "22",
doi = "10.1038/ncomms4603",
language = "English (US)",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}