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The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing

GSE294247 Homo sapiens (human) RNA-seq (gene expression) 110 samples Submitted 2025/06/13 Platform GPL34475Platform GPL24676Platform GPL19057
At a glance

RNA-seq (gene expression) · human · 110 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
Homo sapiens (human)
Samples
110 samples: 30 conditions, mostly with about 4 replicates eachGroups 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
The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicingiScience · 2025
Summary (written by the submitters)
Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it is unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). We used depletion of CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation to interrogate the impact of DIs.
Read the full summary ↓
We found that disruption of Sm protein methylation is sufficient to induce DI upregulation, cell cycle defects, and loss of viability. Finally, we discovered that PRMT5-regulated DIs, and the impacted genes, are highly conserved across human, and also mouse, cell lines but display little interspecies conservation. Despite this, human and mouse DIs have convergent impacts on proliferation by affecting essential components of proliferation-regulating complexes. Together, these data argue that the PRMT5-splicing axis, and particularly appropriate DI splicing, underlies cancer’s vulnerability to PRMT5 inhibitors.
Published in
The PRMT5-splicing axis is a critical oncogenic vulnerability that regulates detained intron splicing
Fowler CE, O'Hearn NA, Salus GJ et al. · iScience 2025 · PMID 40687829 · doi:10.1016/j.isci.2025.112965
This dataset
Open GSE294247 in finder → Find more 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 GSE294247_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 PRJNA1248869 and SRA study SRP577674. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40687829) ↗
Study design
30 conditions, mostly with about 4 replicates each
U87, DMSO-treated, ×4 U87, JNJ-treated, ×4 HCT116, DMSO-treated, ×4 HCT116, JNJ-treated, ×4 PANC1, DMSO-treated, ×4 PANC1, JNJ-treated, ×4 H23, DMSO-treated, ×4 H23, JNJ-treated, ×4 +22 more

Supports a between-group comparison across 110 samples.

How we read this: 30 replicated groups read from 110 sample titles; they account for 110 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

+ 70 more — browse all 110 samples with per-sample file links →

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