Clinical Transplant Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Trends Mol Med. 2021 Jul;27(7):643-659. doi: 10.1016/j.molmed.2021.04.005. Epub 2021 May 13.
RNA splicing is the enzymatic process by which non-protein coding sequences are removed from RNA to produce mature protein-coding mRNA. Splicing is thereby a major mediator of proteome diversity as well as a dynamic regulator of gene expression. Genetic alterations disrupting splicing of individual genes or altering the function of splicing factors contribute to a wide range of human genetic diseases as well as cancer. These observations have resulted in the development of therapies based on oligonucleotides that bind to RNA sequences and modulate splicing for therapeutic benefit. In parallel, small molecules that bind to splicing factors to alter their function or modify RNA processing of individual transcripts are being pursued for monogenic disorders as well as for cancer.
RNA 剪接是一种酶促过程，通过该过程，非蛋白编码序列从 RNA 中被去除，从而产生成熟的蛋白编码 mRNA。因此，剪接是蛋白质组多样性的主要介导者，也是基因表达的动态调节剂。破坏单个基因剪接或改变剪接因子功能的遗传改变导致了广泛的人类遗传疾病以及癌症。这些观察结果导致了基于寡核苷酸的治疗方法的发展，这些寡核苷酸与 RNA 序列结合，调节剪接以获得治疗益处。与此同时，正在探索与剪接因子结合以改变其功能或修饰单个转录物的 RNA 加工的小分子，用于治疗单基因疾病以及癌症。
