Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.
Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.
复制标题
在心血管发育和先天性心脏缺陷中通过选择性剪接和致病性剪接变体进行的转录后修饰。
DOI：
10.3390/ijms24021555
复制
发表时间：
2023-01-13
影响因子：
5.6
通讯作者：
Touma, Marlin
中科院分区：
文献类型：
--
作者：
Mehta, Zubin;Touma, Marlin
关键词：
基因组学、生物信息学和基因组编辑的进步揭示了基因调控的新维度。 mRNA 转录物选择性剪接引起的转录后修饰是哺乳动物基因表达的关键调节机制。在内心深处，人们对阐明选择性剪接在转录组调控中的作用越来越感兴趣。人们付出了大量的努力来研究心脏发育和衰竭的这一过程。然而，很少有研究揭示选择性剪接产品及其在先天性心脏缺陷 (CHD) 中的失调。虽然精美的报告显示了 RNA 结合蛋白 (RBP) 在心脏发育和衰竭过程中协调剪接转变中的关键作用，但 RBP 失调或遗传变异对 CHD 的影响尚未得到充分解决。在此，我们回顾了目前对选择性剪接和 RBP 在心脏发育和 CHD 中的作用的理解。我们讨论围产期剪接转变及其失调对先心病的影响。我们进一步总结了与先天性心脏病有关的关键转录因子中因果剪接变异的发现。更好地了解选择性剪接在心脏发育和先心病中的作用可能会为患有先心病的新生儿提供新的预防和治疗进展。
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.
登录
查看更多内容
影响因子：
11.8
作者：
Gan, Peiheng;Wang, Zhaoning;Morales, Maria Gabriela;Zhang, Yu;Bassel-Duby, Rhonda;Liu, Ning;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
12.3
作者：
Cereda M;Pozzoli U;Rot G;Juvan P;Schweitzer A;Clark T;Ule J
通讯作者：
Ule J
DOI：
10.1073/pnas.96.11.6125
发表时间：
1999-05-25
影响因子：
11.1
作者：
Eldridge, AG;Li, Y;Blencowe, BJ
通讯作者：
Blencowe, BJ
影响因子：
3.9
作者：
Awad, Mark M;Dalal, Darshan;Judge, Daniel P
通讯作者：
Judge, Daniel P
影响因子：
10.8
作者：
Beqqali, Abdelaziz;Bollen, Ilse A. E.;Pinto, Yigal M.
通讯作者：
Pinto, Yigal M.