Role of splicing variants in heart failure

在日本，慢性心力衰竭患者的数量正在增加。发现心力衰竭的新靶点是很重要的。众所周知，选择性剪接在癌症和神经退行性疾病等多种疾病的调控中发挥着重要作用。然而，选择性剪接在心力衰竭发病机制中的作用尚不清楚。在这项研究中，我们使用外显子阵列分析了心力衰竭剪接变异体的整体表达水平。我们发现了46个剪接模式有显著变化但表达水平没有变化的基因。在46个导致心力衰竭的候选基因中，我们将重点缩小到Mtus1基因。我们的功能分析表明，Mtus1A突变体是一种新的心肌肥厚抑制因子。

Number of patients with chronic heart failure is increasing in Japan. It is important to detect novel targets for heart failure. Alternative splicing is known to play important roles in the regulations of several diseases such as cancer and neurodegenerative diseases. However, the role of alternative splicing in the pathogenesis of heart failure remains unclear. In this study, we analyzed global expression levels of splicing variants in heart failure using exon arrays. We identified 46 genes with significant changes in splicing pattern but without changes in expression level. Out of 46 candidate genes responsible for heart failure, we narrowed our focus to Mtus1 gene. Our functional analyses revealed that Mtus1A variant is a novel inhibitory factor for cardiac hypertrophy.