GSE276986
GSE GEO Potentially relatedAging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Relations
Summary
Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged healthy donors directly into neurons, which retained their aging markers. Here we show that aged neurons are broadly depleted of RNA-binding proteins, especially spliceosome components. Intriguingly, splicing proteins â like the dementia and ALS-associated protein TDP-43 â mislocalize to the cytoplasm in aged neurons, which leads to widespread alternative splicing. Cytoplasmic spliceosome components typically are recruited to stress granules, but aged neurons suffer from chronic stress that prevents this sequestration. We link chronic stress to the malfunctioning ubiquitylation machinery, poor HSP90α chaperone activity, and the failure to respond to new stress events. Together our data demonstrates that aging-linked deterioration of RNA biology is a key driver of poor resiliency in aged neurons.
Overall Design
NGS RNA-seq of isogenic transdifferentiated and iPSC-derived neurons before, immediately after, and 24 h after acute stress treatment with 0.5 mM sodium arsenite; deep sequencing was also performed for pre-stress conditions
Analysis (1 step)
View Data Processing- RNA-Seq data was processed using the NF-Core architecture, which compiles several RNA-seq processing steps into a single executable command
Supplementary Files (2)
Potentially Related Publications (1)
This accession was text-mined from the PMC full text of these publications. It may be referenced for comparison or reused from another study rather than generated for them.
Data Files (10)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | NGN_U_C_S26_L001_R1_001.fastq.gz | RNA-Seq | 1.7 GB | link | |||
| — | NK_0_A_S12_L001_R1_001.fastq.gz | RNA-Seq | 308.4 MB | link | |||
| — | NK_0_B_S13_L001_R1_001.fastq.gz | RNA-Seq | 412.3 MB | link | |||
| — | NK_0_C_S14_L001_R1_001.fastq.gz | RNA-Seq | 500.4 MB | link | |||
| — | NK_24_A_S9_L001_R1_001.fastq.gz | RNA-Seq | 456.2 MB | link | |||
| — | NK_24_B_S10_L001_R1_001.fastq.gz | RNA-Seq | 720.1 MB | link | |||
| — | NK_24_C_S11_L001_R1_001.fastq.gz | RNA-Seq | 717.8 MB | link | |||
| — | NK_U_A_S15_L001_R1_001.fastq.gz | RNA-Seq | 1.1 GB | link | |||
| — | NK_U_B_S16_L001_R1_001.fastq.gz | RNA-Seq | 889.6 MB | link | |||
| — | NK_U_C_S17_L001_R1_001.fastq.gz | RNA-Seq | 315.5 MB | link |