GEO series

RNF25 confers tolerance to azacytidine-induced mRNA damage by curbing activation of the integrated stress response [RNA-seq]

GSE313818 Homo sapiens (human) RNA-seq (gene expression) 45 samples Submitted 2026/03/23 Platform GPL30173

At a glance

RNA-seq (gene expression) · human · 45 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)
Topic: Myelodysplastic syndromesThis series is part of our curated briefing on it.
Samples: 45 samples: 15 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.
Paper: RNF25 confers mRNA damage tolerance by curbing activation of the integrated stress responseMolecular cell · 2026

Summary (written by the submitters)

Excessive RNA damage activates cellular stress responses, triggering cell death. However, pathways that negatively regulate RNA damage responses are largely uncharacterized. Using genetic screens, we here find that the ubiquitin ligase RNF25 provides tolerance to RNA damage caused by the nucleoside analogue azacytidine, a chemotherapeutic agent used to treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Read the full summary ↓

Mechanistically, azacytidine is incorporated into mRNA, where it causes lesions that stall elongating ribosomes , leading to cytotoxic activation of the GCN2-dependent integrated stress response (ISR). RNF25 prevents ISR hyperactivation by ubiquitylation of ribosomal protein eS31, suppresses cell death upon azacytidine tretament. Our study reveals an mRNA damage tolerance mechanism that determines cellular survival in response to azacytidine, highlighting RNA damage-induced stress response as a potentially critical component of chemosensitivity in AML and MDS.

Published in

RNF25 confers mRNA damage tolerance by curbing activation of the integrated stress response

Zhao S, Palma-Chaundler CS, Engel CM et al. · Molecular cell 2026 · PMID 41875887 · doi:10.1016/j.molcel.2026.02.024

This dataset

Open GSE313818 in finder → Find more human RNA-seq datasets → Myelodysplastic syndromes landscape →

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 GSE313818_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 PRJNA1381637 and SRA study SRP655311. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41875887) ↗

Study design

15 conditions, mostly in triplicate

AAVS1, untreated, biol ×3 RNF25 KO, untreated, biol ×3 GCN2 KO, untreated, biol ×3 RNF25 GCN2 DKO, untreated, biol ×3 ZNF598 KO, untreated, biol ×3 AAVS1, 4h azaC, biol ×3 RNF25 KO, 4h azaC, biol ×3 GCN2 KO, 4h azaC, biol ×3 +8 more

Supports a between-group comparison across 44 samples.

How we read this: 15 replicated groups read from 45 sample titles; they account for 44 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

GSM9376031 AAVS1, untreated, biol rep1 AAVS1, untreated, biol
GSM9376032 RNF25 KO, untreated, biol rep1 RNF25 KO, untreated, bi…
GSM9376033 GCN2 KO, untreated, biol rep1 GCN2 KO, untreated, biol
GSM9376034 RNF25 GCN2 DKO, untreated, biol rep1 RNF25 GCN2 DKO, untreat…
GSM9376035 ZNF598 KO, untreated, biol rep1 ZNF598 KO, untreated, b…
GSM9376036 eS31_K113R, untreated, biol rep1
GSM9376037 AAVS1, 4h azaC, biol rep1 AAVS1, 4h azaC, biol
GSM9376038 RNF25 KO, 4h azaC, biol rep1 RNF25 KO, 4h azaC, biol
GSM9376039 GCN2 KO, 4h azaC, biol rep1 GCN2 KO, 4h azaC, biol
GSM9376040 RNF25 GCN2 DKO, 4h azaC, biol rep1 RNF25 GCN2 DKO, 4h azaC…
GSM9376041 ZNF598 KO, 4h azaC, biol rep1 ZNF598 KO, 4h azaC, biol
GSM9376042 eS31 K113R, 4h azaC, biol rep1 eS31 K113R, 4h azaC, bi…
GSM9376043 AAVS1, 4h HF, biol rep1 AAVS1, 4h HF, biol
GSM9376044 RNF25 KO, 4h HF, biol rep1 RNF25 KO, 4h HF, biol
GSM9376045 GCN2 KO, 4h HF, biol rep1 GCN2 KO, 4h HF, biol
GSM9376046 AAVS1, untreated, biol rep2 AAVS1, untreated, biol
GSM9376047 RNF25 KO, untreated, biol rep2 RNF25 KO, untreated, bi…
GSM9376048 GCN2 KO, untreated, biol rep2 GCN2 KO, untreated, biol
GSM9376049 RNF25 GCN2 DKO, untreated, biol rep2 RNF25 GCN2 DKO, untreat…
GSM9376050 ZNF598 KO, untreated, biol rep2 ZNF598 KO, untreated, b…
GSM9376051 eS32_K223R, untreated, biol rep2 eS32_K223R, untreated, …
GSM9376052 AAVS1, 4h azaC, biol rep2 AAVS1, 4h azaC, biol
GSM9376053 RNF25 KO, 4h azaC, biol rep2 RNF25 KO, 4h azaC, biol
GSM9376054 GCN2 KO, 4h azaC, biol rep2 GCN2 KO, 4h azaC, biol
GSM9376055 RNF25 GCN2 DKO, 4h azaC, biol rep2 RNF25 GCN2 DKO, 4h azaC…
GSM9376056 ZNF598 KO, 4h azaC, biol rep2 ZNF598 KO, 4h azaC, biol
GSM9376057 eS31 K113R, 4h azaC, biol rep2 eS31 K113R, 4h azaC, bi…
GSM9376058 AAVS1, 4h HF, biol rep2 AAVS1, 4h HF, biol
GSM9376059 RNF25 KO, 4h HF, biol rep2 RNF25 KO, 4h HF, biol
GSM9376060 GCN2 KO, 4h HF, biol rep2 GCN2 KO, 4h HF, biol
GSM9376061 AAVS1, untreated, biol rep3 AAVS1, untreated, biol
GSM9376062 RNF25 KO, untreated, biol rep3 RNF25 KO, untreated, bi…
GSM9376063 GCN2 KO, untreated, biol rep3 GCN2 KO, untreated, biol
GSM9376064 RNF25 GCN2 DKO, untreated, biol rep3 RNF25 GCN2 DKO, untreat…
GSM9376065 ZNF598 KO, untreated, biol rep3 ZNF598 KO, untreated, b…
GSM9376066 eS32_K223R, untreated, biol rep3 eS32_K223R, untreated, …
GSM9376067 AAVS1, 4h azaC, biol rep3 AAVS1, 4h azaC, biol
GSM9376068 RNF25 KO, 4h azaC, biol rep3 RNF25 KO, 4h azaC, biol
GSM9376069 GCN2 KO, 4h azaC, biol rep3 GCN2 KO, 4h azaC, biol
GSM9376070 RNF25 GCN2 DKO, 4h azaC, biol rep3 RNF25 GCN2 DKO, 4h azaC…

+ 5 more — browse all 45 samples with per-sample file links →

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