Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nuclear speckle specific hnRNP DL loss lead to aging associated-cognitive decline by modulating MAPT alternative splicing

ABSTRACT: We report the high-throughput sequencing for differential alternative splicing analyzation in hnRNP DL knockdown and control mice

ORGANISM(S): Mus musculus

PROVIDER: GSE169281 | GEO | 2021/09/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nuclear speckle specific hnRNP DL loss lead to aging associated-cognitive decline by modulating MAPT alternative splicing

Project description:Nuclear speckle specific hnRNP DL loss lead to aging associated-cognitive decline by modulating MAPT alternative splicing

| PRJNA716167 | ENA

Nuclear speckle specific hnRNP D-like prevents age- and AD-related cognitive decline by modulating RNA splicing.

Project description:BackgroundAberrant alternative splicing plays critical role in aging and age-related diseases. Heterogeneous nuclear ribonucleoproteins (hnRNPs) reportedly regulate RNA splicing process. Whether and how hnRNPs contribute to age-related neurodegenerative diseases, especially Alzheimer's disease (AD), remain elusive.MethodsImmunoblotting and immunostaining were performed to determine expression patterns and cellular/subcellular localization of the long isoform of hnRNP D-like (L-DL), which is a hnRNP family member, in mouse hippocampus. Downregulation of L-DL in WT mice was achieved by AAV-mediated shRNA delivery, followed by memory-related behavioural tests. L-DL interactome was analysed by affinity-precipitation and mass spectrometry. Alternative RNA splicing was measured by RNA-seq and analyzed by bioinformatics-based approaches. Downregulation and upregulation of L-DL in APP/PS1 mice were performed using AAV-mediated transduction.ResultsWe show that L-DL is specifically localized to nuclear speckles. L-DL levels are decreased in the hippocampus of aged mouse brains and downregulation of L-DL impairs cognition in mice. L-DL serves as a structural component to recruit other speckle proteins, and regulates cytoskeleton- and synapse-related gene expression by altering RNA splicing. Mechanistically, these splicing changes are modulated via L-DL-mediated interaction of SF3B3, a core component of U2 snRNP, and U2AF65, a U2 spliceosome protein that guides U2 snRNP's binding to RNA. In addition, L-DL levels are decreased in APP/PS1 mouse brains. While downregulation of L-DL deteriorates memory deficits and overexpression of L-DL improves cognitive function in AD mice, by regulating the alternative splicing and expression of synaptic gene CAMKV.ConclusionsOur findings define a molecular mechanism by which hnRNP L-DL regulates alternative RNA splicing, and establish a direct role for L-DL in AD-related synaptic dysfunction and memory decline.

| S-EPMC8456587 | biostudies-literature

Pseudomonas sp. DL strain:DL

Project description:Pseudomonas sp. DL strain:DL Genome sequencing

| PRJNA1186688 | ENA

Blastocystis sp. DL isolate:DL

Project description:Blastocystis sp. DL isolate:DL Genome sequencing

| PRJNA1084795 | ENA

hnRNP R negatively regulates transcription by modulating the association of P-TEFb with 7SK and BRD4

Project description:The P-TEFb complex promotes transcription elongation by releasing paused RNA polymerase II. P-TEFb itself is known to be inactivated through binding to the non-coding RNA 7SK but there is only limited information about mechanisms regulating their association. Here, we show that cells deficient in the RNA-binding protein hnRNP R, a known 7SK interactor, exhibit increased transcription due to phosphorylation of RNA polymerase II. Intriguingly, loss of hnRNP R promotes the release of P-TEFb from 7SK, accompanied by enhanced hnRNP A1 binding to 7SK. Additionally, we found that hnRNP R interacts with BRD4, and that hnRNP R depletion increases BRD4 binding to the P-TEFb component CDK9. Finally, CDK9 is stabilized upon loss of hnRNP R and its association with Cyclin K is enhanced. Together, our results indicate that hnRNP R negatively regulates transcription by modulating the activity and stability of the P-TEFb complex, exemplifying the multimodal regulation of P-TEFb by an RNA-binding protein.

2022-07-21 | GSE202720 | GEO

Mycobacterium sp. DL strain:DL

Project description:Mycobacterium cursimius DL Genome sequencing and assembly

| PRJNA1108959 | ENA

hnRNP A1 iCLIP

Project description:hnRNP A1 iCLIP

| PRJEB9546 | ENA

hnRNP A1 iCLIP

Project description:This experiment identifies hnRNP A1 binding sites transcriptome-wide in Hela cells. HeLa cells with inducible expression of T7-tagged hnRNP A1 were grown to approximately 90% confluence and then subject to iCLIP analysis (following the protocol from Huppertz et al. 2014 (iCLIP: protein-RNA interactions at nucleotide resolution)). The iCLIP library was sequenced using Illumina's HighSeq 1500

2016-06-23 | E-MTAB-3612 | biostudies-arrayexpress

Ogataea parapolymorpha DL-1

Project description:Ogataea parapolymorpha DL-1 Genome sequencing

| PRJNA61171 | ENA

Clostridium sp. DL-VIII

Project description:Clostridium sp. DL-VIII genome sequencing

| PRJNA42093 | ENA