School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka 831-8501, Japan.
Gene. 2022 Apr 15;818:146203. doi: 10.1016/j.gene.2022.146203. Epub 2022 Jan 29.
Amyotrophic lateral sclerosis (ALS) has been considered as one of the progressive neurodegenerative diseases. Numerous genetic factors in divergent molecular pathways have been identified as causative factors of ALS. However, the underlying molecular mechanism that causes this disease remains undetermined; as a result, this has driven the search to find consensus disease-specific hallmarks. In this study, we focused on the alteration of the ratio of two specific gene-splicing events in the SNRNP70 gene from RNA-seq data derived from patients with ALS and control subjects. The splicing profile was significantly and specifically changed in one previously identified ALS subtype. Conversely, the gene expression profile of other ALS cases containing a splicing alteration in the SNRNP70 gene was similar to that of the subtype, whereas ALS cases without this change have exhibited less similarity. These results indicate that this splicing event in the SNRNP70 gene could represent a novel and broadly applicable molecular hallmark of a subtype of ALS.
肌萎缩侧索硬化症（ALS）被认为是一种进行性神经退行性疾病。众多不同分子途径中的遗传因素已被确定为 ALS 的致病因素。然而，导致这种疾病的确切分子机制仍未确定；因此，这促使人们寻找共识的疾病特异性特征。在这项研究中，我们专注于从 ALS 患者和对照受试者的 RNA-seq 数据中，SNRNP70 基因中两种特定基因剪接事件的比值变化。在一个先前确定的 ALS 亚型中，剪接谱发生了显著和特异性变化。相反，SNRNP70 基因中存在剪接改变的其他 ALS 病例的基因表达谱与该亚型相似，而没有这种变化的 ALS 病例则不太相似。这些结果表明，SNRNP70 基因中的这种剪接事件可能代表 ALS 亚型的一个新的和广泛适用的分子特征。
