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IRE1 drives a homeostatic response to reduced protein influx into the endoplasmic reticulum (ISR Timecourse)

GSE323963 Homo sapiens (human) RNA-seq (gene expression) 72 samples Submitted 2026/03/09 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 72 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
72 samples: 24 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)
IRE1, alongside ATF6 and PERK, orchestrates the unfolded protein response, a network of signaling pathways that maintains endoplasmic reticulum (ER) homeostasis. Two modes of IRE1 activation are known: i) in response to an accumulation of unfolded proteins in the ER lumen and ii) in response to compositional changes to the ER membrane that alter its physical properties.
Read the full summary ↓
Here, we identify a third, independent mode of IRE1 activation: ER co-translational translocation deficits activate IRE1 through a mechanism that relies on the release of IRE1 molecules from unoccupied translocons. We define this mechanism as TRES for “TRanslocon Engagement Surveillance”. TRES leads to spontaneous activation of IRE1 and bypasses its unfolded protein- and ER membrane composition-sensing functions. Inhibiting translation initiation similarly activates IRE1 by TRES, as it leads to a decline in ER protein import, thus linking the integrated stress response (ISR) to IRE1 signaling. Surprisingly, TRES drives IRE1 activation without activating ATF6 or PERK, resulting in a distinct gene expression program that feeds back into the co-translational translocation pathway to rebalance the ER protein load. Our findings demonstrate that monitoring and adjusting the rates of protein translocation are critical for maintaining ER homeostasis.
This dataset
Open GSE323963 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 GSE323963_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 PRJNA1432774 and SRA study SRP681228. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
24 conditions, mostly in triplicate
FKBP-PKR Dimerizer (0hrs) ×3 FKBP-PKR Dimerizer (2hrs) ×3 FKBP-PKR Dimerizer (4hrs) ×3 FKBP-PKR Dimerizer (8hrs) ×3 FKBP-PKR Dimerizer (16hrs) ×3 FKBP-PKR Dimerizer (24hrs) ×3 FKBP-PKR 4u8C + Dimerizer (0hrs) ×3 FKBP-PKR 4u8C + Dimerizer (2hrs) ×3 +16 more

Supports a between-group comparison across 72 samples.

How we read this: 24 replicated groups read from 72 sample titles; they account for 72 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

+ 32 more — browse all 72 samples with per-sample file links →

Datasets on a similar topic

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