GEO series

The integrated stress response finetunes 18S nonfunctional rRNA decay (selective Ribo-Seq)

GSE255781 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2025/02/26 Platform GPL30882

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: 8 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 integrated stress response regulates 18S nonfunctional rRNA decay in mammalsMolecular cell · 2025

Summary (written by the submitters)

18S nonfunctional rRNA decay (NRD) detects and eliminates translationally nonfunctional 18S rRNA. The underlying mechanisms associated with the detection and turnover of nonfunctional 18S rRNA remain elusive. While NRD has been identified and exclusively studied in Saccharomyces cerevisiae, it is unclear whether this quality control pathway exists in mammals.

Read the full summary ↓

Here we demonstrate the conservation of 18S NRD in mammalian cells. Using genome-wide CRISPR genetic interaction screens, we identify two molecular events triggered by nonfunctional 18S rRNA— activation of the integrated stress response (ISR) and ubiquitination of ribosomal proteins elicited by GCN2 and RNF10, respectively. Selective ribosome profiling reveals nonfunctional 18S rRNA induces translation arrest at start sites. Biochemical analyses show that activation of the ISR limits translation initiation, attenuating collisions between scanning 43S preinitiation complexes and nonfunctional 80S ribosomes arrested at start sites. Thus, the ISR facilitates the turnover of nonfunctional 18S rRNA and 40S ribosomal proteins by RNF10-mediated ubiquitination. Altogether, these results establish a dynamic feedback mechanism by which cells finetune translation initiation to enable ribosome functionality surveillance through the GCN2-RNF10 axis.

Published in

The integrated stress response regulates 18S nonfunctional rRNA decay in mammals

Coria AR, Shah A, Shafieinouri M et al. · Molecular cell 2025 · PMID 39947182 · doi:10.1016/j.molcel.2025.01.017

This dataset

Open GSE255781 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 GSE255781_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 PRJNA1076517 and SRA study SRP489731. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39947182) ↗

Study design

8 conditions, mostly in duplicate

WT18SWTIPm ×3 WT18SA1824CIPm ×3 WT18SWTIPd ×2 WT18SA1824CIPd ×2 gcn2KO18SA1824CIPd ×2 gcn2KO18SWTIPd ×2 gcn2KO18SA1824CIPm ×2 gcn2KO18SWTIPm ×2

Supports a between-group comparison across 18 samples.

How we read this: 8 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

GSM8079975 WT18SWTIPd1 WT18SWTIPd
GSM8079976 WT18SWTIPd2 WT18SWTIPd
GSM8079977 WT18SA1824CIPd1 WT18SA1824CIPd
GSM8079978 WT18SA1824CIPd2 WT18SA1824CIPd
GSM8079979 gcn2KO18SA1824CIPd1 gcn2KO18SA1824CIPd
GSM8079980 gcn2KO18SA1824CIPd2 gcn2KO18SA1824CIPd
GSM8079981 gcn2KO18SWTIPd1 gcn2KO18SWTIPd
GSM8079982 gcn2KO18SWTIPd2 gcn2KO18SWTIPd
GSM8079983 WT18SWTIPm3 WT18SWTIPm
GSM8079984 WT18SA1824CIPm3 WT18SA1824CIPm
GSM8079985 WT18SWTIPm1 WT18SWTIPm
GSM8079986 WT18SA1824CIPm1 WT18SA1824CIPm
GSM8079987 WT18SWTIPm2 WT18SWTIPm
GSM8079988 WT18SA1824CIPm2 WT18SA1824CIPm
GSM8079989 gcn2KO18SA1824CIPm1 gcn2KO18SA1824CIPm
GSM8079990 gcn2KO18SA1824CIPm2 gcn2KO18SA1824CIPm
GSM8079991 gcn2KO18SWTIPm1 gcn2KO18SWTIPm
GSM8079992 gcn2KO18SWTIPm2 gcn2KO18SWTIPm

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GSE273600 Transcriptomics of specific activation of the Integrated Stress Response compared to Arsenite and Thapsigargin treatment 120 samples shares integrated, stress
GSE241261 Integrated analysis of transcriptional and metabolic responses to mitochondrial stress 72 samples shares integrated, stress
GSE281960 Investigational eIF2B activator DNL343 modulates the Integrated Stress Response in Preclinical Models of TDP-43 Pathology. 70 samples shares integrated, stress
GSE256237 The G3BP Stress-Granule Proteins Reinforce the Translation Program of the Integrated Stress Response 68 samples shares integrated, stress
GSE273601 Transcriptomics of varying strength and timing of specific activation of the Integrated Stress Response 60 samples shares integrated, stress

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