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A noncanonical cytoplasmic role for BUB1 in restraining DNA damage-induced dsRNA accumulation and viral mimicry within stress granules [RNA-seq]

GSE246123 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/10/18 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 2 × B16F10 cells, vector control, no treatment, vs 2 × B16F10 cells, Bub1KO, no treatment, vs 2 × B16F10 cells, vector control, radiation, vs 2 × B16F10 cells, Bub1KO, radiation,Groups 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.
Summary (written by the submitters)
BUB1 is a nuclear serine/threonine protein kinase and a vital spindle assembly checkpoint (SAC) complex member responsible for proper chromosome segregation before mitosis. Here we report that BUB1 plays an unexpected cytoplasmic role in restraining DNA damage-induced accumulation of cytoplasmic dsRNA and ensuing immune response. We showed that tumors deficient in BUB1 were sensitive to radiotherapy in a CD8+T-cell-dependent manner.
Read the full summary ↓
Furthermore, we discovered increased immune cell infiltration accompanied by elevated type I interferon production from irradiated BUB1-deficient cells, caused by enhanced cytoplasmic dsRNA accumulation and activation of the MDA5/MAVS/IRF7 dsRNA-sensing pathway. Mechanistically, we discovered that after exposure to ionizing radiation, BUB1 underwent a robust nucleus-to-cytoplasm migration, where it bound and phosphorylated the polyA-binding protein PABPC1, which was degraded together with its associated mRNAs stored in the stress granules, thereby preventing dsRNA accumulation and activation of the innate immune response. Our study, therefore, reveals a novel biological role for BUB1 in suppressing DNA-damage-induced cytoplasmic dsRNA accumulation/viral mimicry and provides a rationale for inhibiting BUB1 to enhance cytotoxic cancer therapy immunologically.
This dataset
Open GSE246123 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 GSE246123_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 PRJNA1031601 and SRA study SRP468165. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
2 × B16F10 cells, vector control, no treatment, vs 2 × B16F10 cells, Bub1KO, no treatment, vs 2 × B16F10 cells, vector control, radiation, vs 2 × B16F10 cells, Bub1KO, radiation,

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 8 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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