Hassan Fasilat Oluwakemi, Hoque Md Monirul, Majid Abdul, Gbadegoye Joy Olaoluwa, Raafat Amr, Lebeche Djamel
Department of Physiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Cells. 2025 Aug 19;14(16):1283. doi: 10.3390/cells14161283.
This review highlights the emerging functional implications of nonsense-mediated mRNA decay (NMD) in human diseases, with a focus on its therapeutic potential for cardiovascular disease. NMD, conserved from yeast to humans, is involved in apoptosis, autophagy, cellular differentiation, and gene expression regulation. NMD is a highly conserved surveillance mechanism that degrades mRNAs containing premature termination codons (PTCs) located upstream of the final exon-exon junction. NMD serves to prevent the translation of aberrant mRNA and prevents the formation of defective protein products that could result in diseases. Key players in this pathway include up-frameshift proteins (UPFs), nonsense-mediated mRNA decay associated with p13K-related kinases (SMGs), and eukaryotic release factors (eRFs), among others. Dysregulation of NMD has been linked to numerous pathological conditions such as dilated cardiomyopathy, cancer, viral infections, and various neurodevelopmental and genetic disorders. This review will examine the regulatory mechanisms by which NMD regulation or dysregulation may contribute to disease mitigation or progression and its potential for cardiovascular disease therapy. We will further explore how modulating NMD could prevent the outcomes of mutations underlying genetically induced cardiovascular conditions and its applications in personalized medicine due to its role in gene regulation. While recent advances have provided valuable insights into NMD machinery and its therapeutic potential, further studies are needed to clarify the precise roles of key NMD components in cardiovascular disease prevention and treatment.
本综述重点介绍了无义介导的mRNA衰变（NMD）在人类疾病中新兴的功能意义，重点关注其在心血管疾病治疗方面的潜力。NMD从酵母到人类都高度保守，参与细胞凋亡、自噬、细胞分化和基因表达调控。NMD是一种高度保守的监测机制，可降解含有位于最后一个外显子-外显子连接上游的提前终止密码子（PTC）的mRNA。NMD有助于防止异常mRNA的翻译，并防止可能导致疾病的有缺陷蛋白质产物的形成。该途径中的关键分子包括移码上调蛋白（UPF）、与p13K相关激酶相关的无义介导的mRNA衰变（SMG）和真核释放因子（eRF）等。NMD的失调与多种病理状况有关，如扩张型心肌病、癌症、病毒感染以及各种神经发育和遗传疾病。本综述将研究NMD调节或失调可能导致疾病缓解或进展的调控机制及其在心血管疾病治疗中的潜力。我们将进一步探讨调节NMD如何预防遗传诱导的心血管疾病潜在突变的后果，以及由于其在基因调控中的作用，其在个性化医学中的应用。虽然最近的进展为NMD机制及其治疗潜力提供了有价值的见解，但仍需要进一步研究以阐明关键NMD成分在心血管疾病预防和治疗中的精确作用。
