Mus musculus
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ABSTRACT:
PROVIDER: PRJNA292620 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression profiling of neurons with Rbfox1 and Rbfox3 knockdown and rescue with cytoplasmic or nuclear Rbfox1 isoform [RNA-seq]
| PRJNA292447 | ENA
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from microarray experiments. We performed microarray analysis to profile gene expression and splicing changes in mouse hippocampal cultures (14 DIV) with Rbfox1 and Rbfox3 double knockdown by siRNAs. Before the treatment of siRNAs, the hippocampal cultures were treated with AraC to eliminate glial cells and co-cultured with cortical cultures to support the growth of neurons. Six samples were analyzed.
2015-12-10 | E-GEOD-71974 | biostudies-arrayexpress
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from RNA-seq experiments. We performed RNA-seq to profile gene expression and splicing changes. The expression levels of Rbfox1 and Rbfox3 in cultured mouse hippocampal neurons were reduced by siRNAs. The reduction of Rbfox1 and 3 was rescued by expression of cytoplasmic or nuclear Rbfox1 splice isoform. The gene expression and splicing profiles were compared between different treatments. Eight samples were analyzed.
2015-12-10 | E-GEOD-71916 | biostudies-arrayexpress
Project description:Rbfox1, Rbfox2, and Rbfox3 iCLIP from mouse brain nuclear fractions
| PRJNA307988 | ENA
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from iCLIP-seq experiments. We performed iCLIP procedures to identify Rbfox1 binding in the cytoplasm. Cultured mouse forebrain neurons were irradiated with UV and a cytoplasmic fraction was purified for immunoprecipitation. An anti-Rbfox1 antibody was used to immunoprecipitate Rbfox1 target RNAs and an anti-Flag antibody was used as control. Two samples were analyzed.
2015-12-10 | E-GEOD-71790 | biostudies-arrayexpress
Project description:The direct conversion of human skin fibroblasts to neurons has a low efficiency and unclear mechanism. Here, we show that the knockdown of PTBP2 (nPTB) significantly enhanced the transdifferentiation induced by ASCL1, MiR124-9/9* and p53 shRNA to generate mostly GABAergic neurons. Longitudinal RNAseq analyses identified the continuous induction of many RNA Splicing Regulators (RSRs). Among these, the knockdown of RBFOX3, which encodes the mature neuronal marker NeuN, significantly abrogated the transdifferentiation. Overexpression of RBFOX3 significantly enhanced the conversion induced by AMp; the enhancement was occluded by PTBP2 knockdown. We found that PTBP2 attenuation significantly favored neuron-specific alternative splicing (AS) of many genes involved in synaptic transmission, signal transduction, and axon formation. RBFOX3 knockdown significantly reversed the effect, while RBFOX3 overexpression enhanced it. The study reveals the critical role of neuron-specific AS in the direct conversion of human skin fibroblasts to neurons by showing that PTBP2 attenuation enhances this mechanism in concert with RBFOX3.
2023-10-12 | GSE210131 | GEO
Project description:Dysregulation of the brain-enriched RNA binding protein Rbfox1 has been linked to neurologic diseases such as epilepsy and autism spectrum disorders. However, it remains unexplored how distinct neuronal populations might contribute to neurologic dysfunction resulting from Rbfox1 loss. To examine these issues we profiled gene expression specifically in the hippocampus of wildtype and Rbfox1-/- mice. We identified transcripts whose expression was strongly Rbfox1-dependent and exhibited significant Rbfox1 binding in their 3’UTRs. One prominent target, Vamp1, was found to be specifically expressed in GABAergic interneurons. Both Vamp1 knockdown and Rbfox1 loss led to decreased synaptic transmission, and altered E/I balance in the Rbfox1-/- hippocampus, indicating that Vamp1 loss is a major component of the Rbfox1-/- physiological phenotype. The cytoplasmic isoform of Rbfox1 was sufficient to rescue Vamp1 expression in Rbfox1-/- neurons. We show that Rbfox1 binding in the Vamp1 3’UTR promotes its expression in part by antagonizing the brain-enriched microRNA-9. These results demonstrate that inhibitory neurons maintain specialized synaptic vesicle release machinery containing Vamp1 that is critically regulated by Rbfox1.
2018-04-04 | GSE96722 | GEO
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from microarray experiments.
2015-12-10 | GSE71974 | GEO
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from iCLIP-seq experiments.
2015-12-10 | GSE71790 | GEO
Project description:Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from RNA-seq experiments.
2015-12-10 | GSE71916 | GEO