SFRS8 regulates memory by modulating pre-mRNA splicing of synaptic genes in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1143517 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30114372_1.fastq.gz | Fastqsanger.gz | |||
| SRR30114372_2.fastq.gz | Fastqsanger.gz | |||
| SRR30114373_1.fastq.gz | Fastqsanger.gz | |||
| SRR30114373_2.fastq.gz | Fastqsanger.gz | |||
| SRR30114374_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:SFRS8 is a member of SR family protein. It is also a known splicing factor that is highly expressed in the brain. However, its function in the brain remains elusive. Here, we find that SFRS8 is required to maintain normal synaptic protein levels as well as synaptic densities. Mechanistically, we demonstrate that SFRS8 interacts with SF3B3, a major component of U2 snRNP complex, and regulates the RNA alternative splicing process. Specifically, SFRS8 regulates the levels of PSD95, through enhancing the loading of Psd95 mRNA on the U2 snRNP complex and increasing the skipping of exon18 of Psd95. We further demonstrate that SFRS8 knockdown in the hippocampus leads to reduced synaptic protein expression, decreased spine density, consequently defective memory in mice. Similar reduction in synaptic protein expression and synaptic density are also evident in cultured neurons. Taken together, SFRS8 regulates memory function in mice through altering the alternative splicing and expression of synaptic genes via SFRS8-SF3B3 interaction.
2025-06-06 | GSE273869 | GEO
Project description:Circadian protein TIMELESS regulates synaptic plasticity and memory by modulating cAMP signaling
| PRJNA858471 | ENA
Project description:Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell type-specific AS in a concentration and phosphorylation dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 changes AS of endogenous pre-mRNAs, similar to what was observed upon overexpression of SR proteins. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight a novel role for a nrRNA in the regulation of gene expression. Malat1 Antisense and control knockdowns evaluated on a microarray platform to profile alternative splicing levels for 5782 cassette-type alternative exons.
2010-09-01 | E-GEOD-22963 | biostudies-arrayexpress
Project description:Regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of circadian genes on cellular and molecular mechanisms that influnce synaptic plasticity and cognitive function remain to be identified. Here, we show that conditional deletion of the circadian gene Timeless in the adult forebrain leads to an impairment in working and fear memory in mice. These cognitive phenotypes were accompanied with LTP attenuation of hippocampal Schaffer-collateral synapses. We discovered TIMELESS protein acts as a transcriptional factor regulating phosphodiesterase 4B (PDE4B) expression. Through Pde4b transcription, TIMELESS negatively regulates cAMP signaling to modulate AMPA receptor GluA1 function and fine-tune synaptic plasticity. Our data provide insights into the neuron-specific function of mammalian TIMELESS by defining a mechanism that regulates synaptic plasticity and cognitive function.
2023-04-17 | GSE208149 | GEO
Project description:pre-mRNA splicing in C. elegans
| PRJNA663456 | ENA
Project description:CpG dinucleotides introduced into gag can inhibit HIV-1 gene expression by modulating pre-mRNA splicing
| PRJNA554120 | ENA
Project description:Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity. The serine/arginine (SR) splicing factors regulate tissue- or cell type-specific AS in a concentration and phosphorylation dependent manner. However, the mechanisms that modulate the cellular levels of active SR proteins remain to be elucidated. In the present study, we provide evidence for a role for the long nuclear-retained regulatory RNA (nrRNA), MALAT1 in AS regulation. MALAT1 interacts with SR proteins and influences the distribution of these and other splicing factors in nuclear speckle domains. Depletion of MALAT1 changes AS of endogenous pre-mRNAs, similar to what was observed upon overexpression of SR proteins. Furthermore, MALAT1 regulates cellular levels of phosphorylated forms of SR proteins. Taken together, our results suggest that MALAT1 regulates AS by modulating the levels of active SR proteins. Our results further highlight a novel role for a nrRNA in the regulation of gene expression.
2010-09-01 | GSE22963 | GEO
Project description:Experience-dependent learning depends on synaptic plasticity. Recent findings show that effective integration of novel salient information requires coordinated processes of homo- and hetero- synaptic plasticity onto neighboring dendritic branches. In this work, we hypothesized that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to this mechanism. We show that clusters of the peri-synaptic ECM proteoglycans, containing 6- and 2,6-sulfated chondroitin sulfates recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. CS56 co-immunoprecipitation of synaptosomal proteins identified several CS56-carrying/binding synaptic molecules that are implicated in Ca2+ signaling, vesicles cycling and AMPA-receptor exocytosis, thus suggesting their pivotal role in long-term potentiation (LTP). Finally, we demonstrated that the attenuation of CS56 glycoepitopes in the CA1 hippocampal region, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in adult mice. These findings show that specific ECM glycans regulates the molecular mechanisms underlying induction and consolidation of synaptic plasticity, confirming that experience-dependent refinement of the brain ECM plays a critical role in learning and memory.
2024-05-10 | PXD047129 | Pride
Project description:Synaptic plasticity impairment plays a critical role in the pathogenesis of Alzheimer’s disease (AD), and emerging evidence has shown that microRNAs (miRNAs) are alternative biomarkers and therapeutic targets for synaptic dysfunctions in AD. In this study, we found that the level of miR-431 was downregulated in the plasma of amnestic mild cognitive impairment (aMCI) and AD patients. In addition, it was decreased in the hippocampus and plasma of APPswe/PS1dE9 (APP/PS1) mice. Lentivirus mediated miR-431 overexpression in the hippocampus CA1 ameliorated synaptic plasticity and memory deficits of APP/PS1 mice, while it didn't affect the Aβ levels. Smad4 was identified as a target of miR-431, and Smad4 knockdown modulated the expression of synaptic proteins including SAP102, and protected against synaptic plasticity and memory dysfunctions in APP/PS1 mice. Furthermore, Smad4 overexpression reversed the protective effects of miR-431, indicating that miR-431 attenuated synaptic impairment at least partially by Smad4 inhibition. Thus, these results indicated that miR-431/Smad4 might be a potential therapeutic target for AD treatment.
2023-05-15 | GSE231985 | GEO
Project description:Alternative splicing diversifies mRNA transcripts in human cells. While the spliceosome pairs exons with a high degree of accuracy, the rates of rare aberrant and non-canonical pre-mRNA splicing have not been evaluated at the nucleotide level to determine the quantity and identity of these events across splice junctions. Using ultra-deep sequencing the frequency of aberrant and non-canonical splicing events for three splice junctions flanking exon 7 of SMN1 were determined at single nucleotide resolution. After correction for background noise introduced by PCR amplification and sequencing steps, pre-mRNA splicing was shown to maintain a low overall rate of aberrant and non-canonically spliced events. Several previously unannotated splicing events across 3 exon|intron junctions in SMN1 were identified. Mutations within SMN exon 7 were shown to affect splicing fidelity by modulating RNA secondary structures, by altering the binding site of regulatory proteins and by changing the 5’ splice site strength. Mutations also create a truncated SMN1 exon 7 through the introduction of a de novo non-canonical 5’ splice site. The results from the ultra-deep sequencing approach highlight the impressive fidelity of pre-mRNA splicing and demonstrate that the immediate sequence context around splice sites is the main driving force behind non-canonical splice site pairing.
2019-09-24 | GSE137883 | GEO