Institute of Experimental Cardiology, Heidelberg University Hospital, Heidelberg, Germany.
DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Heidelberg, Germany.
Curr Heart Fail Rep. 2020 Oct;17(5):234-246. doi: 10.1007/s11897-020-00475-x.
This review aims to give an update on recent findings related to the cardiac splicing factor RNA-binding motif protein 20 (RBM20) and RBM20 cardiomyopathy, a form of dilated cardiomyopathy caused by mutations in RBM20.
While most research on RBM20 splicing targets has focused on titin (TTN), multiple studies over the last years have shown that other splicing targets of RBM20 including Ca/calmodulin-dependent kinase IIδ (CAMK2D) might be critically involved in the development of RBM20 cardiomyopathy. In this regard, loss of RBM20 causes an abnormal intracellular calcium handling, which may relate to the arrhythmogenic presentation of RBM20 cardiomyopathy. In addition, RBM20 presents clinically in a highly gender-specific manner, with male patients suffering from an earlier disease onset and a more severe disease progression. Further research on RBM20, and treatment of RBM20 cardiomyopathy, will need to consider both the multitude and relative contribution of the different splicing targets and related pathways, as well as gender differences.
本综述旨在介绍与心脏剪接因子 RNA 结合基序蛋白 20(RBM20)和 RBM20 心肌病相关的最新发现,RBM20 心肌病是一种由 RBM20 突变引起的扩张型心肌病。
虽然大多数关于 RBM20 剪接靶标的研究都集中在肌联蛋白(TTN)上,但近年来的多项研究表明,RBM20 的其他剪接靶标,包括钙/钙调蛋白依赖性激酶 IIδ(CAMK2D),可能在 RBM20 心肌病的发展中起着关键作用。在这方面,RBM20 的缺失导致细胞内钙离子处理异常,这可能与 RBM20 心肌病的致心律失常表现有关。此外,RBM20 以高度性别特异性的方式表现出临床症状,男性患者的疾病发病更早,疾病进展更严重。进一步研究 RBM20 以及 RBM20 心肌病的治疗,需要考虑不同剪接靶标和相关途径的多样性及其相对贡献,以及性别差异。