RBM20-Related Cardiomyopathy: Current Understanding and Future Options

Journal of Clinical Medicine

Michael Gotthardt¹  Lars M. Steinmetz²  Jan Koelemen³  Benjamin Meder³ 

[1] DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10117 Berlin, Germany;DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg, 69120 Heidelberg, Germany;Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany;

关键词: dilated cardiomyopathy;    RBM20;    arrhythmia;    heart failure;    gene therapy;    alternative splicing;   

DOI  :  10.3390/jcm10184101

来源: DOAJ

【 摘 要 】

Splice regulators play an essential role in the transcriptomic diversity of all eukaryotic cell types and organ systems. Recent evidence suggests a contribution of splice-regulatory networks in many diseases, such as cardiomyopathies. Adaptive splice regulators, such as RNA-binding motif protein 20 (RBM20) determine the physiological mRNA landscape formation, and rare variants in the RBM20 gene explain up to 6% of genetic dilated cardiomyopathy (DCM) cases. With ample knowledge from RBM20-deficient mice, rats, swine and induced pluripotent stem cells (iPSCs), the downstream targets and quantitative effects on splicing are now well-defined and the prerequisites for corrective therapeutic approaches are set. This review article highlights some of the recent advances in the field, ranging from aspects of granule formation to 3D genome architectures underlying RBM20-related cardiomyopathy. Promising therapeutic strategies are presented and put into context with the pathophysiological characteristics of RBM20-related diseases.

【 授权许可】

Unknown