Abstract
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.
Highlights
Heart development, and these transitions may have functional importance in human heart development
We presented for the first time, a high-resolution global analysis of alternative splicing (AS) transitions during human heart development
The functional analysis of foetal-specific AS events showed enrichment associated with cell proliferation-related pathways, whereas the adult-specific AS events were associated with protein synthesis
Summary
Heart development, and these transitions may have functional importance in human heart development. No reports have described a genome-wide analysis of AS transitions during human heart development. We comparatively analysed AS and gene expression transitions of the foetal and adult heart using eight publically available RNA-sequencing datasets. We determined whether the genes exhibiting AS transitions were enriched for specific functions. We analysed the correlation of AS transitions and differentially expressed genes between foetal and adult hearts
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