Similar Datasets
Project description:Precise coordination of molecular programs and neuronal growth govern the formation, maintenance, and adaptation of neuronal circuits. RNA metabolism has emerged as a key regulatory node of neural development and nervous system pathologies. To uncover novel cell-type-specific RNA regulators, we systematically investigated expression of RNA recognition motif-containing proteins in the mouse neocortex. Surprisingly, we found RBM20, an alternative splicing regulator associated with dilated cardiomyopathy, to be expressed in cortical parvalbumin interneurons and mitral cells of the olfactory bulb. Genome-wide mapping of RBM20 target mRNAs revealed that neuronal RBM20 binds distal intronic regions. Loss of neuronal RBM20 has only modest impact on alternative splice isoforms but results in a significant reduction in an array of mature mRNAs in the neuronal cytoplasm. This phenotype is particularly pronounced for genes with long introns that encode synaptic proteins. We hypothesize that RBM20 ensures fidelity of pre-mRNA splicing by suppressing non-productive splicing events in long neuronal genes. This work highlights a common requirement of two excitable cell types, cardiomyocytes and neurons, for RBM20-dependent transcriptome regulation.
2023-12-16 | GSE250098 | GEO
Project description:Precise coordination of molecular programs and neuronal growth govern the formation, maintenance, and adaptation of neuronal circuits. RNA metabolism has emerged as a key regulatory node of neural development and nervous system pathologies. To uncover novel cell-type-specific RNA regulators, we systematically investigated expression of RNA recognition motif-containing proteins in the mouse neocortex. Surprisingly, we found RBM20, an alternative splicing regulator associated with dilated cardiomyopathy, to be expressed in cortical parvalbumin interneurons and mitral cells of the olfactory bulb. Genome-wide mapping of RBM20 target mRNAs revealed that neuronal RBM20 binds distal intronic regions. Loss of neuronal RBM20 has only modest impact on alternative splice isoforms but results in a significant reduction in an array of mature mRNAs in the neuronal cytoplasm. This phenotype is particularly pronounced for genes with long introns that encode synaptic proteins. We hypothesize that RBM20 ensures fidelity of pre-mRNA splicing by suppressing non-productive splicing events in long neuronal genes. This work highlights a common requirement of two excitable cell types, cardiomyocytes and neurons, for RBM20-dependent transcriptome regulation.
2023-12-16 | GSE250096 | GEO
Project description:The dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons
| PRJNA1052022 | ENA
Project description:The dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons [seCLIP-Seq]
| PRJNA1052024 | ENA
Project description:The dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons [Ribo-TRAP RNA-seq]
| PRJNA1052025 | ENA
Project description:Backgrounddata on the natural course and prognosis of tachycardia-induced cardiomyopathy (TICMP) and comparison with idiopathic dilated cardiomyopathies (IDCM) are scarce.ObjectiveTo compare the clinical presentation, comorbidities, and long-term outcomes of TICMP patients with IDCM patients.Methodsa retrospective cohort study of patients hospitalized with new-onset TICMP or IDCM. The primary endpoint was a composite of death, myocardial infarction, thromboembolic events, assist device, heart transplantation, and ventricular tachycardia or fibrillation (VT/VF). The secondary endpoint was recurrent hospitalization due to heart failure (HF) exacerbation.Resultsthe cohort was comprised of 64 TICMP and 66 IDCM patients. The primary composite endpoint and all-cause mortality were similar between the groups during a median follow-up of ~6 years (36% versus 29%, p = 0.33 and 22% versus 15%, p = 0.15, respectively). Survival analysis showed no significant difference between TICMP and IDCM groups for the composite endpoint (p = 0.75), all-cause mortality (p = 0.65), and hospitalizations due to heart failure exacerbation. Nonetheless, the incidence of recurrent hospitalization was significantly higher in TICMP patients (incidence rate ratio 1.59; p = 0.009).Conclusionspatients with TICMP have similar long-term outcomes as those with IDCM. However, it portends a higher rate of HF readmissions, mostly due to arrhythmia recurrences.
| S-EPMC9960677 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-16 | GSE241120 | GEO
Project description:To elucidate the role of cardiac myosin-binding protein-C (MyBP-C) in myocardial structure and function, we have produced mice expressing altered forms of this sarcomere protein. The engineered mutations encode truncated forms of MyBP-C in which the cardiac myosin heavy chain-binding and titin-binding domain has been replaced with novel amino acid residues. Analogous heterozygous defects in humans cause hypertrophic cardiomyopathy. Mice that are homozygous for the mutated MyBP-C alleles express less than 10% of truncated protein in M-bands of otherwise normal sarcomeres. Homozygous mice bearing mutated MyBP-C alleles are viable but exhibit neonatal onset of a progressive dilated cardiomyopathy with prominent histopathology of myocyte hypertrophy, myofibrillar disarray, fibrosis, and dystrophic calcification. Echocardiography of homozygous mutant mice showed left ventricular dilation and reduced contractile function at birth; myocardial hypertrophy increased as the animals matured. Left-ventricular pressure-volume analyses in adult homozygous mutant mice demonstrated depressed systolic contractility with diastolic dysfunction. These data revise our understanding of the role that MyBP-C plays in myofibrillogenesis during cardiac development and indicate the importance of this protein for long-term sarcomere function and normal cardiac morphology. We also propose that mice bearing homozygous familial hypertrophic cardiomyopathy-causing mutations may provide useful tools for predicting the severity of disease that these mutations will cause in humans.
| S-EPMC409819 | biostudies-literature
Project description:Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated heart muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, in which Ate1 deletion was driven by α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time, resulting in high rates of lethality after 6months of age. These symptoms were accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the newborns and far preceding the onset of cardiomyopathy, suggesting that these defects were primary and likely underlay the development of the future heart defects. Several major sarcomeric proteins were arginylated in vivo. Moreover, Ate1 deletion in the hearts resulted in a significant reduction of active and passive myofibril forces, suggesting that arginylation is critical for both myofibril structural integrity and contractility. Thus, arginylation is essential for maintaining the heart function by regulation of the major myofibril proteins and myofibril forces, and its absence in the heart muscle leads to progressive heart failure through cardiomyocyte-specific defects.
| S-EPMC3418387 | biostudies-literature