← BioTransfer GEO Dataset Finder
GEO series

MDM2 binds and suppresses RNA polymerase III to restrain the innate immune response to cytosolic DNA

GSE333484 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2026/08/06 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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
18 samples: 6 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.
Summary (written by the submitters)
The oncoprotein MDM2 is widely recognized as the principal negative regulator of p53, thereby controlling the expression of numerous RNA polymerase II (Pol II)-dependent genes involved in cell cycle arrest and apoptosis. Beyond this canonical role, MDM2 also engages in transcriptional regulation independently of p53, for instance through interactions with polycomb repressor complexes.
Read the full summary ↓
Here, we identify RNA polymerase III (Pol III) as an additional target of MDM2 function. Using two complementary chemical tools – a small-molecule MDM2 antagonist (MI-1061) that releases p53 and augments MDM2 expression, and a PROTAC degrader (MD-224) that simultaneously activates p53 and promotes MDM2 ubiquitination and proteasomal destruction – we dissected the role of MDM2 in cells with amplified MDM2. Elevated MDM2 suppressed the transcription of Pol III-dependent genes encoding tRNA or 5S ribosomal RNA. Mechanistically, we found the aminoterminal domain of MDM2 associated with the catalytic subunit of Pol III, revealing a molecular link between MDM2 and the Pol III machinery. Because Pol III also acts as a cytosolic DNA sensor that converts DNA into double-stranded RNA to trigger RIG-I–TBK1–IRF3–dependent signaling, we asked whether MDM2 modulates this pathway. Indeed, enhanced MDM2 expression markedly attenuated the induction of innate immunity genes such as CXCL10, OAS1, and MX1 following transfection with Poly(dA:dT). Similarly, DNA damage induced by a radiomimetic agent activated Pol III–dependent innate signaling, and this was again blunted by high MDM2 levels, resulting in enhanced cell survival. Taken together, our findings establish MDM2 as a previously unrecognized suppressor of Pol III–dependent transcription in response to cytosolic DNA. This expands the repertoire of MDM2 functions beyond repression of p53 and Pol II activity, positioning MDM2 as a broad regulator of transcription and innate immunity.
This dataset
Open GSE333484 in finder → Find more human 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 GSE333484_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 PRJNA1471167 and SRA study SRP704179. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly in triplicate
SJSA-1 cells, DMSO 72h, DMSO 24h, ×3 SJSA-1 cells, DMSO 72h, MD-224 24h, ×3 SJSA-1 cells, DMSO 72h, MI-1061 24h, ×3 SJSA-1 cells, NCS 72h, DMSO 24h, ×3 SJSA-1 cells, NCS 72h, MD-224 24h, ×3 SJSA-1 cells, NCS 72h, MI-1061 24h, ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

Search all human RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.