Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identifying microRNAs that bind to cytoplasmic TDP43

ABSTRACT: Identifying microRNAs that bind to cytoplasmic TDP43

PROVIDER: PRJNA606339 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Identifying microRNAs that bind to cytoplasmic TDP43

Project description:TDP43 is involved in microRNA biogenesis and found in cytoplasmic aggregates in amyotrophic lateral sclerosis (ALS), and microRNAs are important for regulation of gene expression and represent potential biomarkers and therapeutic targets. Therefore, we examined microRNAs that preferentially bind cytoplasmic TDP43 using cellular models expressing TDP43 variants and NanoString miRNA profiling analyses. We identified cytoplasmic TDP43-associated miRNAs and predicted genes and pathways to gain insights into potentially relevant disease pathways, biomarkers, and reversible therapeutic targets for ALS.

2020-04-23 | GSE145214 | GEO

Comprehensive Transcriptomic Analysis of NSC34 Motor Neurons following TDP43 Modulation: Knockdown vs. Control and Wild Type vs. TDP43 M337V Mutation

Project description:Transactive response DNA binding protein of 43 kDa (TDP43) is a ribonucleoprotein integral to several neurodegenerative diseases. Under normal conditions, TDP43 primarily localizes in the nucleus, where it plays a crucial role in RNA metabolism. Its function necessitates shuttling between the nucleus and cytoplasm. TDP43 dysfunction plays a significant role in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and Parkinson’s disease. A common dysfunction of TDP43 is nuclear depletion and cytoplasmic aggregation of the protein. Additionally, aggregation-prone mutations, such as the TDP43M337V mutation, exacerbate TDP43 mislocalization to the cytoplasm, increasing neuronal toxicity. Given TDP43's critical role in RNA processing, its depletion or mutation disrupts the transcriptomic landscape, leading to aberrant RNA processing and splicing. In this study, we employed a library preparation method capturing both coding and noncoding RNA, generating a comprehensive nuclear transcriptomic dataset following TDP43 knockdown or mutant TDP43M337V expression in NSC34 motor neurons. This nuanced strategy significantly enhances our understanding of the intricate interplay between TDP43 dysfunction and the cellular transcriptome, providing valuable insights into the pathogenesis of TDP43 proteinopathies.

2025-06-04 | E-MTAB-13738 | biostudies-arrayexpress

An intramolecular salt bridge linking TDP43’s RNA recognition motifs dictates RNA binding, protein stability and TDP43-dependent neurodegeneration

Project description:The majority of individuals with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) exhibit neuronal cytoplasmic inclusions rich in the RNA binding protein TDP43. Even so, the relationship between TDP43’s RNA binding properties and neurodegeneration remain obscure. Here we show that engineered mutations disrupting a salt bridge between TDP43’s RNA recognition motifs interfere with nucleic acid binding and eliminate recognition of native TDP43 substrates. The accumulation of WT TDP43, but not RNA binding-deficient variants, disproportionately affected the abundance and splicing of encoding ribosome and oxidative phosphorylation components.

2019-03-22 | GSE128647 | GEO

S-acylation of TDP43 regulates its condensation in amyotrophic lateral sclerosis

Project description:TDP43 inclusion bodies are widely present in the majority of patients with familial and sporadic amyotrophic lateral sclerosis (ALS). The mechanisms regulating TDP43 solubility remain incompletely understood. Here, we report that TDP43 undergoes S-acylation primarily at the Cys244 residue by the S-acyltransferase zDHHC23. This S-acylation maintains the liquid-like properties of TDP43 by reducing the aberrant interaction with poly(ADP-ribose) polymerase 1 (PARP1) and PARylated proteins, thereby countering the pathological condensation of TDP43. S-acylation-deficient TDP43 inclusions sequester the translational machinery and inhibit cytoplasmic protein translation, ultimately resulting in neurotoxicity. Importantly, TDP43 S-acylation is decreased in the familial ALS-associated TDP43 mutants as well as in SOD1-G93A mice and C9orf72-ALS induced pluripotent stem cell (iPSC)-derived neurons, suggesting the widespread involvement of TDP43 S-acylation in ALS pathogenesis. Our findings reveal an undescribed modification of TDP43 and provide deeper insight into the regulation of TDP43 pathological condensation in ALS.

2026-05-17 | PXD061643 | Pride

Cytoplasmic TDP43 Binds microRNAs: New Disease Targets in Amyotrophic Lateral Sclerosis.

Project description: Not available

| S-EPMC7235295 | biostudies-literature

Identifying microRNAs and their editing sites in Macaca mulatta

Project description:Identifying microRNAs and their editing sites in Macaca mulatta

| PRJNA511985 | ENA

Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

Project description:Identifying and targeting angiogenesis-related microRNAs in ovarian cancer

| PRJNA493637 | ENA

Sexual dimorphism in ALS-linked TDP43 mice

Project description:TDP43 mice study

| PRJEB86491 | ENA

TDP43 proteinopathy exhibits disease, tissue, and context-specific cryptic splicing signatures

Project description:Mislocalization of the nuclear protein TDP43 is a hallmark of ALS and FTD and leads to de-repression and inclusion of cryptic exons, which represent promising biomarkers of TDP43 pathology. However, most cryptic exons to date have been identified from in vitro models, limiting our understanding of any tissue and/or cell-specific splices. We meta-analyzed published bulk RNA-Seq datasets representing 1,778 RNAseq profiles of ALS and FTD post mortem tissue, and in vitro models with experimentally depleted TDP43. We identified novel cryptic splices and mapped out their tissue-specificity, demonstrating subsets with distinct cortical and spinal cord enrichment. Novel events were validated by RNA-Seq and RT-qPCR in a new spinal cord cohort, and analysis of single-nucleus datasets localized cortical splices to layer-specific neuronal populations. This catalog of cryptic splices is the first step towards the development of biomarkers for cell type-specific TDP43 pathology.

2024-03-28 | GSE255683 | GEO

Rapid and Inducible Mislocalization of Endogenous TDP43 in a Novel Human Model of Amyotrophic Lateral Sclerosis [Nanopore]

Project description:In this study, we describe the development of a new model of TDP43 proteinopathy using human induced pluripotent stem cell (iPSC)-derived neurons. Utilizing a genome engineering approach, we induced the mislocalization of endogenous TDP43 from the nucleus to the cytoplasm without mutating the TDP43 gene or using chemical stressors

2025-03-07 | GSE290441 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data