Key result
Cytoplasmic mutant RBM20 causes murine atrial arrhythmogenicity via a splicing-independent gain-of-function role in DCM.
Why the study?
RBM20 mutations are linked to severe DCM and AF, and recent studies suggest gain of function of mutant RBM20 independent of splicing defects may also contribute to pathogenesis.
Gain of function of mutant RBM20, independent of splicing defects, may play a critical role in the pathogenesis of dilated cardiomyopathy and atrial arrhythmogenicity.
Hypothesis-generating for RBM20 gain-of-function in atrial arrhythmogenicity; leaves open translation to human dilated cardiomyopathy.
RNA binding motif protein 20 (RBM20) is a critical splicing regulator in cardiomyocytes, and mutations in its RSRSP domain are associated with severe dilated cardiomyopathy (DCM) and a high prevalence of atrial fibrillation (AF). RBM20 mutation has long been thought to cause DCM through the disturbed splicing of the target genes by its loss of function. However, recent studies have highlighted that the gain of function of mutant RBM20, independent of splicing defects, may also play a critical role in the pathogenesis of DCM.
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Ihara et al. (2025) studied Dilated cardiomyopathy and atrial fibrillation. Cytoplasmic mutant RBM20 was evaluated on Arrhythmogenicity and pathogenesis of DCM. Cytoplasmic mutant RBM20 causes arrhythmogenicity in murine atria, suggesting a gain-of-function role independent of splicing defects in the pathogenesis of dilated cardiomyopathy.
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