Rare variants in the RBM20 gene explain up to 6% of genetic dilated cardiomyopathy cases, and recent advances in understanding its splicing effects have set prerequisites for therapeutic approaches.
RBM20 variants are a significant cause of genetic dilated cardiomyopathy, and understanding their role in splicing networks is paving the way for targeted therapeutic approaches.
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.
Koelemen et al. (Sat,) conducted a review in RBM20-Related Cardiomyopathy. Rare variants in the RBM20 gene explain up to 6% of genetic dilated cardiomyopathy cases, and recent advances in understanding its splicing effects have set prerequisites for therapeutic approaches.