Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role
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PROVIDER: PRJNA635023 | ENA |
REPOSITORIES: ENA
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Project description:Serine-rich splicing factor 3 (SRSF3) was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte-specific Srsf3 conditional knockout (cKO) mouse model. Fifteen-day-old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced the left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodeling induced by Srsf3 deletion. RNA-seq analysis of the hearts of 5-day-old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I-driven respiration of permeabilized cardiac muscle fibers from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating the mitochondrial integrity.
2021-06-23 | GSE151168 | GEO
Project description:The mitogen-activated protein kinase (MAPK) p38 signaling pathway is essential for normal heart function. However, p38 also contributes to heart failure pathogenesis by affecting heart contractility and cardiomyocyte survival. To unravel the complex cardiac role of p38, we report the interactome of p38α and p38γ, the two well expressed isoforms in the heart, obtained via an APEX proximity assay performed in cultured neonatal rat ventricular myocytes. The p38α and p38γ have distinct interactomes in cardiomyocytes for both studied states; basal and activated by an osmotic stress. Interestingly, the activated p38α interactome contains many spliceosome implicated RNA-binding proteins. The serine/arginine-rich splicing factor 3 (SRSF3) is of particular interest and its interaction with p38α was validated by co-immunoprecipitation. p38 is sufficient to partially relocate nuclear SRSF3 to cytoplasm. The alternative splicing function of SRSF3 is also modulated by the p38 pathway. Our findings reveal a novel set of proteins to investigate in order to decipher cardiac functions of the MAPK p38, as well as a specific regulation mechanism of SRSF3 by p38 in cardiomyocytes.
2021-03-01 | PXD011089 | Pride
Project description:Clinically, cardiac dysfunction is a key component of sepsis-induced multi-organ failure. Mitochondrial function is essential for cardiomyocyte homeostasis as disrupted mitochondrial dynamics enhances mitophagy and apoptosis. However, therapies targeted to improve mitochondrial function in septic patients have not been explored. Our research is helpful to understand the role of cardiomyocyte PPARα in LPS-induced cardiac dysfunction
2023-04-20 | GSE229298 | GEO
Project description:RNA sequencing of adult cardiomyocyte cyclin C deletion
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Project description:Several members of SRSF family play wide-ranging roles in the regulation of transcription and post-splicing processes as well as splice sites selection. Although the expression of SRSF3 was reported to be overexpressed in several cancers, the roles of SRSF3 in the cancer cells are almost unknown. We analyzed differentially expressed genes in SRSF3 siRNA-treated HCT116 cells and identified the specific pathways regulated by SRSF3. After treatment of HCT116 cells with SRSF3 (sample 02) or control (sample 01) siRNA, total RNA was extracted using RNeasy Mini Kit (Qiagen, Valencia, CA). The quality of the purified RNA and its applicability for microarray analysis were assessed by the Agilent 2100 Bioanalyzer using a RNA 6000 Nano Labchip kit (Agilent Technologies, Palo Alto, CA, USA). Total RNA (400 ng) was used for amplification, labeling and hybridization to a whole human genome oligoDNA microarray (4x44k; Agilent) according to the manufacture’s instructions.
2013-08-04 | E-GEOD-31876 | biostudies-arrayexpress
Project description:The goal of this study is to analyse the transcriptome of control hearts vs hearts lacking SRSF3 expression and to analyse binding preferences of SRSF3 in cardiac myocytes.
2019-05-27 | GSE123002 | GEO
Project description:RNA sequencing was performed to identify gene expression changes following SRSF3 depletion in mouse bone marrow megakaryocytes and peripheral blood platelets.
2021-12-21 | GSE155620 | GEO
Project description:Several members of SRSF family play wide-ranging roles in the regulation of transcription and post-splicing processes as well as splice sites selection. Although the expression of SRSF3 was reported to be overexpressed in several cancers, the roles of SRSF3 in the cancer cells are almost unknown. We analyzed differentially expressed genes in SRSF3 siRNA-treated HCT116 cells and identified the specific pathways regulated by SRSF3.
2013-08-04 | GSE31876 | GEO
Project description:SRSF3 is overexpressed in human invasive ovarian cancer and its overexpression is required for cancer cell growth and survival. To decipher the mechnisms behind the role of SRSF3 in ovarian cancer, we examined the gene expression and splicing in the ovarian cancer cell line that was engineered to express a doxycycline-induced SRSF3 siRNA, which was able to knockdown SRSF3 expression by 90% and induce apoptosis. Total RNAs extracted from A2780/SRSF3si2, a subline of ovarian cancer cell line A2780, treated with or without doxycycline at 0.1ug/ml for three days were analyzed using Affymetrix GeneChip® Human Exon 1.0 ST Array
2015-08-06 | E-GEOD-71745 | biostudies-arrayexpress
Project description:Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.
2018-07-30 | GSE95142 | GEO