Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA291362 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Bronx waltzer mutation in Srrm4, a gene that encodes a neuronal Ser/Arg (SR)-rich splicing factor, disrupts the expression of several alternative exons specifically in the inner ear. Here we show that the expression of SRRM3 in neurons limits the distribution of SRRM4-dependent splicing. In vitro, SRRM3 and SRRM4 regulated the same alternative exons, yet in vivo Srrm3 deficiency caused neuronal splicing alterations and motor dysfunction, indicating that SRRM3 has non-redundant functions. Mice harboring mutations in both Srrm3 and Srrm4 failed to breathe, and their neuromuscular junctions (NMJ) were malformed. Transcriptome-wide analysis revealed a large network of SRRM3/SRRM4-dependent splicing changes, including the skipping of key exons in the NMJ organizer Agrin. Furthermore, SRRM3/SRRM4 regulated gene expression through neuron-specific switches in chromatin regulatory complexes and by altering the reading frame in several mRNAs. Our findings reveal that the SRRM3/SRRM4 subfamily of SR proteins is central to regulation of the neuronal transcriptome. In this dataset, we include probe-set level data obtained from brain cortex samples. The processed data represent probe-set intensities that have been normalized to gene expression levels.
2018-07-01 | GSE71480 | GEO
Project description:The Bronx waltzer mutation in Srrm4, a gene that encodes a neuronal Ser/Arg (SR)-rich splicing factor, disrupts the expression of several alternative exons specifically in the inner ear. Here we show that the expression of SRRM3 in neurons limits the distribution of SRRM4-dependent splicing. In vitro, SRRM3 and SRRM4 regulated the same alternative exons, yet in vivo Srrm3 deficiency caused neuronal splicing alterations and motor dysfunction, indicating that SRRM3 has non-redundant functions. Mice harboring mutations in both Srrm3 and Srrm4 failed to breathe, and their neuromuscular junctions (NMJ) were malformed. Transcriptome-wide analysis revealed a large network of SRRM3/SRRM4-dependent splicing changes, including the skipping of key exons in the NMJ organizer Agrin. Furthermore, SRRM3/SRRM4 regulated gene expression through neuron-specific switches in chromatin regulatory complexes and by altering the reading frame in several mRNAs. Our findings reveal that the SRRM3/SRRM4 subfamily of SR proteins is central to regulation of the neuronal transcriptome. In this dataset, we include probe-set level data obtained from cerebellar samples. The processed data represent probe-set intensities that have been normalized to gene expression levels.
2018-07-01 | GSE71479 | GEO
Project description:MJAY analysis of cerebellar RNA obtained from Srrm3 gene-trapped mice and wild-type mice
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Project description:To investigate the role of MSI1, SRRM3 and SRRM4 as a regulator of retina microexons (RetMICs) in vitro in humans, we have ectopically expressed these genes in HEK293 cells and performed RNA-seq.
2022-07-01 | GSE180779 | GEO
Project description:Neuroendocrine (NE) differentiation in metastatic castration-resistant prostate cancer (mCRPC) usually develops through cellular plasticity. We recently characterized two mCRPC phenotypes with NE features; Androgen receptor (AR)-positive, NE-positive amphicrine prostate cancer (AMPC) and AR-negative small cell or neuroendocrine prostate cancer (SCNPC). Here, we interrogate the RE-1 silencing transcription factor (REST) pathway in mCRPC and demonstrate that SRRM3 has analogous functions to SRRM4 and mediates NE differentiation through alternative splicing of REST. We scrutinize transcriptome datasets across species and tumor types and discover that SRRM3 and SRRM4 expression define molecular phenotypes in AMPC and SCNPC. Notably, we characterize two AMPC phenotypes driven by either REST attenuation or ASCL1 activity and three SCNPC phenotypes with progressive activation of neuronal transcription factor programs. Together, our data provides a biological framework for classifying NE phenotypes in mCRPC that could be useful for future therapeutic development and precision medicine applications.
2021-07-14 | GSE158598 | GEO
Project description:Neuroendocrine (NE) differentiation in metastatic castration-resistant prostate cancer (mCRPC) usually develops through cellular plasticity. We recently characterized two mCRPC phenotypes with NE features; Androgen receptor (AR)-positive, NE-positive amphicrine prostate cancer (AMPC) and AR-negative small cell or neuroendocrine prostate cancer (SCNPC). Here, we interrogate the RE-1 silencing transcription factor (REST) pathway in mCRPC and demonstrate that SRRM3 has analogous functions to SRRM4 and mediates NE differentiation through alternative splicing of REST. We scrutinize transcriptome datasets across species and tumor types and discover that SRRM3 and SRRM4 expression define molecular phenotypes in AMPC and SCNPC. Notably, we characterize two AMPC phenotypes driven by either REST attenuation or ASCL1 activity and three SCNPC phenotypes with progressive activation of neuronal transcription factor programs. Together, our data provides a biological framework for classifying NE phenotypes in mCRPC that could be useful for future therapeutic development and precision medicine applications.
2021-07-14 | GSE158593 | GEO
Project description:Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and its abnormal function causes diabetes or hypoglycemia. Here, we uncover a conserved program of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural program that are particularly sensitive to the levels of this protein. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, SRRM3 mutant mice display defects in islet cell identity and function, leading to hyperinsulinemic hypoglycemia. Importantly, human genetic variants that influence SRRM3 expression and microexon inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk.
2022-12-14 | GSE198906 | GEO
Project description:Transcriptome analysis of cortical excitatory neurons of juvenile brain in wild-type and Nipbl mutant mice
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