PDF(Pubmed)
Abstract：
Advancements in genomics, bioinformatics, and genome editing have uncovered new dimensions in gene regulation. Post-transcriptional modifications by the alternative splicing of mRNA transcripts are critical regulatory mechanisms of mammalian gene expression. In the heart, there is an expanding interest in elucidating the role of alternative splicing in transcriptome regulation. Substantial efforts were directed toward investigating this process in heart development and failure. However, few studies shed light on alternative splicing products and their dysregulation in congenital heart defects (CHDs). While elegant reports showed the crucial roles of RNA binding proteins (RBPs) in orchestrating splicing transitions during heart development and failure, the impact of RBPs dysregulation or genetic variation on CHDs has not been fully addressed. Herein, we review the current understanding of alternative splicing and RBPs\' roles in heart development and CHDs. Wediscuss the impact of perinatal splicing transition and its dysregulation in CHDs. We further summarize the discoveries made of causal splicing variants in key transcription factors that are implicated in CHDs. An improved understanding of the roles of alternative splicing in heart development and CHDs may potentially inform novel preventive and therapeutic advancements for newborn infants with CHDs.
摘要：
基因组学的进步，生物信息学，和基因组编辑揭示了基因调控的新维度。通过mRNA转录物的可变剪接进行的转录后修饰是哺乳动物基因表达的关键调节机制。在心中,人们对阐明可变剪接在转录组调控中的作用越来越感兴趣。大量努力致力于研究心脏发育和衰竭的这一过程。然而,很少有研究阐明选择性剪接产物及其在先天性心脏病（CHD）中的失调。虽然优雅的报告显示RNA结合蛋白（RBP）在协调心脏发育和衰竭期间的剪接转换中的关键作用，尚未完全解决RBPs失调或遗传变异对CHD的影响。在这里，我们回顾了目前对选择性剪接和RBPs在心脏发育和CHD中作用的理解。我们讨论围产期剪接转换及其失调在CHD中的影响。我们进一步总结了与CHD有关的关键转录因子中因果剪接变体的发现。对选择性剪接在心脏发育和CHD中的作用的更好理解可能为CHD新生婴儿提供新的预防和治疗进展。
