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Suppression of the mRNA export pathway dampens viral mimicry response and promotes tumor immune evasion [RNA-seq]

GSE250590 Mus musculus (mouse) RNA-seq (gene expression) 92 samples Submitted 2025/06/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 92 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
92 samples: 40 conditions, mostly in duplicateGroups 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 mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcriptsScience translational medicine · 2025
Summary (written by the submitters)
Transcriptional induction of retroelement transcripts through therapeutic interventions elevates cytosolic double-stranded RNA (dsRNA) levels to trigger viral mimicry response and anti-tumor immunity. Therapeutic interventions that transcriptionally induce retroelement transcripts lead to elevated levels of cytosolic double-stranded RNA (dsRNA), thereby triggering a viral mimicry response and enhancing anti-tumor immunity.
Read the full summary ↓
Despite the promising implications, clinical studies have revealed substantial variations in the therapeutic induction of viral mimicry response in different cancer patients, with the underlying mechanisms remaining largely elusive. In this study, we illuminate the pivotal role of the mRNA export pathway in viral mimicry response and anti-tumor T cell immunity. Notably, epigenetic and posttranscriptional induction of cytosolic dsRNAs necessitates the mRNA export pathway to transport the nuclear-transcribed retroelement transcripts into the cytoplasm, which is posttranscriptionally suppressed by the RNA exosome in coactivator-associated arginine methyltransferase 1 (CARM1)-expressing tumor cells. Mechanistically, Carm1 restricts the nuclear export of retroelement transcripts through transcriptional elevation and posttranslational stabilization of the RNA exosome, which hydrolyzes the critical nuclear RNA export adaptor transcripts Ddx39a and Alyref. Collectively, our study underscores the vital importance of the mRNA export pathway in viral mimicry response and suggests that enhancing its activity through Carm1 or RNA exosome inhibition could reinforce therapy-induced viral mimicry response, thus holding the potential to overcome tumor immune escape and immunotherapy resistance.
Published in
The mRNA export pathway licenses viral mimicry response and antitumor immunity by actively exporting nuclear retroelement transcripts
Wang X, Jin J, Yan H et al. · Science translational medicine 2025 · PMID 40203080 · doi:10.1126/scitranslmed.ado4370
This dataset
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.

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 GSE250590_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1054587 and SRA study SRP478948. Searching any of these in the dataset finder brings you back here.

Study design
40 conditions, mostly in duplicate
Carm1-knockout B16-F10 cells, sgCtrl, ×4 Carm1-knockout B16-F10 cells Cytoplasm, sgCtr… ×4 Carm1-knockout B16-F10 cells Nuclear, sgCtrl, ×4 B16-F10 cells, sgCtrl treated with Decitabine, ×4 B16-F10 cells Cytoplasm, sgCtrl treated with … ×4 B16-F10 cells Nuclear, sgCtrl treated with De… ×4 Sorted B16-F10 cells, wild-type, ×2 Sorted B16-F10 cells, sgCarm1, ×2 +32 more

Supports a case/control comparison: 26 samples read as cases, 18 as controls.

How we read this: 40 replicated groups read from 92 sample titles; they account for 92 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

+ 52 more — browse all 92 samples with per-sample file links →

Datasets on a similar topic

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