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TDP-43 directly inhibits RNA accumulation in neurites through modulation of RNA stability

GSE288185 Mus musculus (mouse) RNA-seq (gene expression) 86 samples Submitted 2025/02/01 Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 86 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
86 samples: 28 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stabilityThe EMBO journal · 2026
Summary (written by the submitters)
The subcellular localization of hundreds of RNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for the vast majority of these RNAs, the mechanisms that govern their localization are unknown. Here we demonstrate that the ALS-associated RNA binding protein TDP-43 primarily acts to keep RNAs out of neuronal projections.
Read the full summary ↓
Using subcellular fractionation and single molecule FISH we find that TDP-43 loss results in the increased neurite accumulation of hundreds of RNAs. These RNAs were highly enriched for known TDP-43 binding sites, suggesting that TDP-43 directly binds them to regulate their localization. We then identified precise regions within them that mediate their TDP-43-dependent localization and interaction with TDP-43 using high-throughput functional assays in cells and high-throughput binding assays in vitro. We found that these regions also mediated TDP-43-dependent RNA instability, identifying the mechanism by which TDP-43 regulates RNA localization. ALS-associated mutations in TDP-43 resulted in similar RNA mislocalization phenotypes as did TDP-43 loss in human iPS-derived motor neurons. These findings establish TDP-43 as a direct negative regulator of RNA abundance in neurites and suggest that mislocalization of specific transcripts may occur in ALS patients.
Published in
TDP-43 directly inhibits mRNA accumulation in neurites through modulation of mRNA stability
Moffatt C, Arora A, Vaeth KF et al. · The EMBO journal 2026 · PMID 41398473 · doi:10.1038/s44318-025-00653-4
This dataset
Open GSE288185 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE288185_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1216540 and SRA study SRP560349. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41398473) ↗
Study design
28 conditions, mostly in triplicate
MPRA Neurite -dox ×4 MPRA Neurite +dox ×4 MPRA Soma -dox ×4 MPRA Soma +dox ×4 CAD Neurite -dox ×3 CAD Neurite +dox ×3 CAD Soma -dox ×3 CAD Soma +dox ×3 +22 more

Supports a between-group comparison across 84 samples.

How we read this: 28 replicated groups read from 86 sample titles; they account for 84 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 46 more — browse all 86 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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