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Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modifications [ISO-seq]

GSE279460 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/01/02 Platform GPL29177
At a glance

RNA-seq (gene expression) · mouse · 16 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
16 samples: 4 × Male_LongRead_Striatum_NT vs 4 × Male_LongRead_Striatum_HD vs 4 × Male_LongRead_Cortex_NT vs 4 × Male_LongRead_Cortex_HDGroups 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
Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modificationNature neuroscience · 2025
Summary (written by the submitters)
Huntington’s disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here, we identify the RNA-binding TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.
Read the full summary ↓
Dysregulated nuclear localization of TDP-43 and cytoplasmic accumulation of phosphorylated TDP-43 is shown to be present in HD mice and human brains with TDP-43 co-localizing with HTT nuclear aggregate-like bodies distinct from mutant HTT inclusions and from previously observed TDP-43 pathologies. The binding of TDP-43 onto RNAs encoding HD-associated differentially expressed and aberrantly spliced genes is decreased. Finally, m6A RNA modification is reduced on RNAs abnormally expressed in the striatum from HD R6/2 mouse brain, including at clustered sites adjacent to TDP-43 binding sites. Our evidence supports TDP-43 loss of function coupled with altered m6A modification as a mechanism underlying alternative splicing in HD and highlights the critical nature of TDP-43 loss of function across multiple neurodegenerative diseases.
Published in
Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification
Nguyen TB, Miramontes R, Chillon-Marinas C et al. · Nature neuroscience 2025 · PMID 39762660 · doi:10.1038/s41593-024-01850-w
This dataset
Open GSE279460 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 GSE279460_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 PRJNA1167771 and SRA study SRP536087. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39762660) ↗
Study design
4 × Male_LongRead_Striatum_NT vs 4 × Male_LongRead_Striatum_HD vs 4 × Male_LongRead_Cortex_NT vs 4 × Male_LongRead_Cortex_HD

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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
Datasets on a similar topic

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