Genome-wide analysis of alternative splicing during human heart development

被引：0
作者：
He Wang
Yanmei Chen
Xinzhong Li
Guojun Chen
Lintao Zhong
Gangbing Chen
Yulin Liao
Wangjun Liao
Jianping Bin
机构：
[1] State Key Laboratory of Organ Failure Research,Department of Cardiology
[2] Nanfang Hospital,Department of Cardiology
[3] Southern Medical University,Department of Oncology
[4] Second Affiliated Hospital of Nanchang University,undefined
[5] Nanfang Hospital,undefined
[6] Southern Medical University,undefined
来源：
Scientific Reports | / 6卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Alternative splicing (AS) drives determinative changes during mouse heart development. Recent high-throughput technological advancements have facilitated genome-wide AS, while its analysis in human foetal heart transition to the adult stage has not been reported. Here, we present a high-resolution global analysis of AS transitions between human foetal and adult hearts. RNA-sequencing data showed extensive AS transitions occurred between human foetal and adult hearts, and AS events occurred more frequently in protein-coding genes than in long non-coding RNA (lncRNA). A significant difference of AS patterns was found between foetal and adult hearts. The predicted difference in AS events was further confirmed using quantitative reverse transcription-polymerase chain reaction analysis of human heart samples. Functional foetal-specific AS event analysis showed enrichment associated with cell proliferation-related pathways including cell cycle, whereas adult-specific AS events were associated with protein synthesis. Furthermore, 42.6% of foetal-specific AS events showed significant changes in gene expression levels between foetal and adult hearts. Genes exhibiting both foetal-specific AS and differential expression were highly enriched in cell cycle-associated functions. In conclusion, we provided a genome-wide profiling of AS transitions between foetal and adult hearts and proposed that AS transitions and deferential gene expression may play determinative roles in human heart development.
引用
收藏
相关论文
共 112 条
  • [1] Olson EN(2006)Gene regulatory networks in the evolution and development of the heart Science 313 1922-1927
  • [2] Steinhauser ML(2011)Regeneration of the heart EMBO Mol Med 3 701-712
  • [3] Lee RT(2011)Cardiac muscle regeneration: lessons from development Genes Dev 25 299-309
  • [4] Mercola M(2013)Mammalian heart renewal by pre-existing cardiomyocytes Nature 493 433-436
  • [5] Ruiz-Lozano P(2012)Functional screening identifies miRNAs inducing cardiac regeneration Nature 492 376-381
  • [6] Schneider MD(2012)RBM20, a gene for hereditary cardiomyopathy, regulates titin splicing Nat Med 18 766-773
  • [7] Senyo SE(2013)Sequencing of mRNA identifies re-expression of foetal splice variants in cardiac hypertrophy J Mol Cell Cardiol 62 99-107
  • [8] Eulalio A(2003)Mechanisms of alternative pre-messenger RNA splicing Annu Rev Biochem 72 291-336
  • [9] Guo W(2008)Alternative isoform regulation in human tissue transcriptomes Nature 456 470-476
  • [10] Ames EG(2007)Functional coordination of alternative splicing in the mammalian central nervous system Genome Biol 8 R108-1415
12345678910