Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
Laboratory of Molecular Medicinal Science, Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga 525-8577, Japan.
Int J Mol Sci. 2021 Jul 21;22(15):7789. doi: 10.3390/ijms22157789.
Pre-mRNA splicing is an essential process for gene expression in higher eukaryotes, which requires a high order of accuracy. Mutations in splicing factors or regulatory elements in pre-mRNAs often result in many human diseases. Myelodysplastic syndrome (MDS) is a heterogeneous group of chronic myeloid neoplasms characterized by many symptoms and a high risk of progression to acute myeloid leukemia. Recent findings indicate that mutations in splicing factors represent a novel class of driver mutations in human cancers and affect about 50% of Myelodysplastic syndrome (MDS) patients. Somatic mutations in MDS patients are frequently found in genes , , and . Interestingly, they are involved in the recognition of 3' splice sites and exons. It has been reported that mutations in these splicing regulators result in aberrant splicing of many genes. In this review article, we first describe molecular mechanism of pre-mRNA splicing as an introduction and mainly focus on those four splicing factors to describe their mutations and their associated aberrant splicing patterns.
前体 mRNA 剪接是高等真核生物基因表达的一个必要过程，需要高度的准确性。剪接因子或前体 mRNA 中调节元件的突变常导致许多人类疾病。骨髓增生异常综合征 (MDS) 是一组异质性的慢性髓系肿瘤，其特征是多种症状和向急性髓系白血病进展的高风险。最近的研究结果表明，剪接因子的突变代表了人类癌症中一种新的驱动突变类型，影响了大约 50%的 MDS 患者。在 MDS 患者中，体细胞突变经常发生在基因、和中。有趣的是，它们参与了 3' 剪接位点和外显子的识别。据报道，这些剪接调节因子的突变导致许多基因的异常剪接。在这篇综述文章中，我们首先描述了前体 mRNA 剪接的分子机制作为介绍，并主要集中在这四个剪接因子上，描述它们的突变及其相关的异常剪接模式。
