Nguyen Khue Vu
a Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego , San Diego , CA , USA.
b Department of Pediatrics, UC San Diego School of Medicine , La Jolla , CA , USA.
Nucleosides Nucleotides Nucleic Acids. 2019;38(10):752-780. doi: 10.1080/15257770.2019.1594893. Epub 2019 May 11.
The purpose of this review is to highlight the impact of the alternative splicing process on human disease. Epigenetic regulation determines not only what parts of the genome are expressed but also how they are spliced. The recent progress in the field of epigenetics has important implications for the study of rare diseases. The role of epigenetics in rare diseases is a key issue in molecular physiology and medicine because not only rare diseases can benefit from epigenetic research, but can also provide useful principles for other common and complex disorders such as cancer, cardiovascular, type 2 diabetes, obesity, and neurological diseases. Predominantly, epigenetic modifications include DNA methylation, histone modification, and RNA-associated silencing. These modifications in the genome regulate numerous cellular activities. Disruption of epigenetic regulation process can contribute to the etiology of numerous diseases during both prenatal and postnatal life. Here, I discuss current knowledge about this matter including some current epigenetic therapies and future directions in the field by emphasizing on the RNA-based therapy via antisense oligonucleotides to correct splicing defects.
本综述的目的是强调可变剪接过程对人类疾病的影响。表观遗传调控不仅决定基因组的哪些部分会表达，还决定它们如何进行剪接。表观遗传学领域的最新进展对罕见病研究具有重要意义。表观遗传学在罕见病中的作用是分子生理学和医学中的一个关键问题，因为不仅罕见病能从表观遗传学研究中受益，还能为其他常见和复杂疾病（如癌症、心血管疾病、2型糖尿病、肥胖症和神经疾病）提供有用的原理。主要地，表观遗传修饰包括DNA甲基化、组蛋白修饰和RNA相关的沉默。基因组中的这些修饰调节着众多细胞活动。表观遗传调控过程的破坏在产前和产后生活中都可能导致多种疾病的病因。在此，我将讨论关于这一问题的当前知识，包括一些当前的表观遗传疗法以及该领域的未来方向，重点是通过反义寡核苷酸进行基于RNA的疗法来纠正剪接缺陷。
