Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
RNA splicing contributes to a broad spectrum of post-transcriptional gene regulation during normal development, as well as pathological manifestation of heart diseases. However, the functional role and regulation of splicing in heart failure remain poorly understood. RNA binding protein (RBP), a major component of the splicing machinery, is a critical factor in this process.
RNA binding motif protein 24
(
RBM24
) is a tissue-specific RBP which is highly expressed in human and mouse heart. Previous studies demonstrated the functional role of
RBM24
in the embryonic heart development. However, the role of
RBM24
in postnatal heart development and
heart disease
has not been investigated. In this paper, using conditional
RBM24
knockout mice, we demonstrated that ablation of
RBM24
in postnatal heart led to rapidly progressive dilated cardiomyopathy (DCM), heart failure, and postnatal lethality. Global splicing profiling revealed that
RBM24
regulated a network of genes related to cardiac function and diseases. Knockout of
RBM24
resulted in misregulation of these splicing transitions which contributed to the subsequent development of cardiomyopathy. Notably, our analysis identified
RBM24
as a splice factor that determined the splicing switch of a subset of genes in the sacomeric Z-disc complex, including Titin, the major disease gene of DCM and heart failure. Together, this study identifies regulation of RNA splicing by
RBM24
as a potent player in remodeling of heart during postnatal development, and provides novel mechanistic insights to the pathogenesis of DCM.
...
PMID:RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy. 3042 57
