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Pharmacological Targeting of RIG-I Selectively Activates the Integrated Stress Response

GSE254965 Homo sapiens (human) RNA-seq (gene expression) 11 samples Submitted 2025/09/26 Platform GPL28038
At a glance

RNA-seq (gene expression) · human · 11 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
11 samples: 11 samples, each with a distinct title — no replicated groupsGroups 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
Pharmacological targeting of RIG-I can selectively activate the integrated stress responseScience advances · 2025
Summary (written by the submitters)
The integrated stress response (ISR) is a eukaryotic pathway that attenuates global protein synthesis while allowing selective translation of specific mRNAs, which together can reestablish homeostasis following an acute stress. Diverse pathologic insults activate one or more of the four ISR kinases, which selectively phosphorylate eIF2a to induce translational and transcriptional adaptation of multiple biological functions.
Read the full summary ↓
Recent results suggest that enhancing ISR kinase activity could ameliorate pathologies linked to numerous diseases, including many neurodegenerative disorders. However, few pharmacological strategies exist to selectively activate ISR kinases and downstream adaptive signaling. Here, we describe compound A8 and its cyclized metabolite CC81 as highly-selective ISR activators that activate the heme-regulated inhibitor (HRI) ISR kinase through a mechanism involving binding of the cytosolic pattern recognition receptor RIG-I. Our results establish a pharmacological strategy to selectively activate HRI-dependent ISR signaling by targeting RIG-I, revealing new mechanistic options for ameliorating etiologically diverse diseases through ISR activation.
Published in
Pharmacological targeting of RIG-I can selectively activate the integrated stress response
Cuoco CA, Ren W, Baron KR et al. · Science advances 2025 · PMID 41160678 · doi:10.1126/sciadv.adt3014
This dataset
Open GSE254965 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 GSE254965_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 PRJNA1072711 and SRA study SRP487816. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41160678) ↗
Study design
11 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 11 sample titles: 11 distinct titles with little repetition. 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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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.