Faculty of Environment and Life, Beijing University of Technology, Xueyuan Road, Haidian District, Beijing 100124, PR China.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77573, USA.
Cardiovasc Res. 2023 Jun 13;119(6):1324-1335. doi: 10.1093/cvr/cvad014.
Cleavage and polyadenylation of pre-mRNAs is a necessary step for gene expression and function. Majority of human genes exhibit multiple polyadenylation sites, which can be alternatively used to generate different mRNA isoforms from a single gene. Alternative polyadenylation (APA) of pre-mRNAs is important for the proteome and transcriptome landscape. APA is tightly regulated during development and contributes to tissue-specific gene regulation. Mis-regulation of APA is linked to a wide range of pathological conditions. APA-mediated gene regulation in the heart is emerging as a new area of research. Here, we will discuss the impact of APA on gene regulation during heart development and in cardiovascular diseases. First, we will briefly review how APA impacts gene regulation and discuss molecular mechanisms that control APA. Then, we will address APA regulation during heart development and its dysregulation in cardiovascular diseases. Finally, we will discuss pre-mRNA targeting strategies to correct aberrant APA patterns of essential genes for the treatment or prevention of cardiovascular diseases. The RNA field is blooming due to advancements in RNA-based technologies. RNA-based vaccines and therapies are becoming the new line of effective and safe approaches for the treatment and prevention of human diseases. Overall, this review will be influential for understanding gene regulation at the RNA level via APA in the heart and will help design RNA-based tools for the treatment of cardiovascular diseases in the future.
前体 mRNA 的剪接和多聚腺苷酸化是基因表达和功能所必需的步骤。大多数人类基因表现出多个多聚腺苷酸化位点，这些位点可以被交替使用，从单个基因产生不同的 mRNA 异构体。前体 mRNA 的可变多聚腺苷酸化（APA）对蛋白质组和转录组景观很重要。APA 在发育过程中受到严格调控，并有助于组织特异性基因调控。APA 的失调与广泛的病理状况有关。APA 介导的心脏基因调控正成为一个新的研究领域。在这里，我们将讨论 APA 对心脏发育和心血管疾病中基因调控的影响。首先，我们将简要回顾 APA 如何影响基因调控，并讨论控制 APA 的分子机制。然后，我们将讨论心脏发育过程中的 APA 调节及其在心血管疾病中的失调。最后，我们将讨论针对前体 mRNA 的靶向策略，以纠正心血管疾病中必需基因的异常 APA 模式，从而达到治疗和预防的目的。由于 RNA 技术的进步，RNA 领域正在蓬勃发展。基于 RNA 的疫苗和疗法正成为治疗和预防人类疾病的有效和安全方法的新途径。总的来说，这篇综述将有助于理解心脏中通过 APA 进行的 RNA 水平的基因调控，并有助于设计未来用于治疗心血管疾病的基于 RNA 的工具。
