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Optogenetic Clustering of Human IRE1 Reveals Differential Regulation of Transcription and mRNA Splice Isoform Abundance by the UPR

GSE302406 Homo sapiens (human) RNA-seq (gene expression) 39 samples Submitted 2025/07/16 Platform GPL26167
At a glance

RNA-seq (gene expression) · human · 39 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
39 samples: 13 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
Direct optical activation of human IRE1 identifies unique patterns of transcriptional and post-transcriptional mRNA regulation in the unfolded protein responseThe Journal of biological chemistry · 2026
Summary (written by the submitters)
Inositol-requiring enzyme 1 (IRE1) is one of three known sensor proteins that respond to homeostatic perturbations in the metazoan endoplasmic reticulum. The three sensors collectively initiate an intertwined signaling network called the Unfolded Protein Response (UPR). Although IRE1 plays pivotal roles in human health and development, understanding its specific contributions to the UPR remains a challenge due to signaling crosstalk from the other two stress sensors.
Read the full summary ↓
To overcome this problem, we engineered a light-activatable version of IRE1 and probed the transcriptomic effects of IRE1 activity in isolation from the other branches of the UPR. We demonstrate that 1) oligomerization alone is sufficient to activate IRE1 in human cells, 2) IRE1’s transcriptional response evolves substantially under prolonged activation, and 3) the UPR induces major changes in mRNA splice isoform abundance in an IRE1-independent manner. Our data reveal previously unknown targets of IRE1 transcriptional regulation and direct degradation. Additionally, the tools developed here will be broadly applicable for precise dissection of signaling networks in diverse cell types, tissues, and organisms.
Published in
Direct optical activation of human IRE1 identifies unique patterns of transcriptional and post-transcriptional mRNA regulation in the unfolded protein response
Smith JW, Wilburn DB, Belyy V · The Journal of biological chemistry 2026 · PMID 41421490 · doi:10.1016/j.jbc.2025.111067
This dataset
Open GSE302406 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 GSE302406_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 PRJNA1290351 and SRA study SRP600214. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41421490) ↗
Study design
13 conditions, mostly in triplicate
U-2 OS WT, baseline 0 hours, ×3 U-2 OS Opto-IRE1, baseline 0 hours, ×3 U-2 OS WT, blue light 6 hours, ×3 U-2 OS Opto-IRE1, blue light 6 hours, ×3 U-2 OS Opto-IRE1, blue light 2 hours, ×3 U-2 OS Opto-IRE1, blue light 24 hours, ×3 U-2 OS WT, 5µg/mL tunicamycin 2 hours, ×3 U-2 OS Opto-IRE1, 5µg/mL tunicamycin 2 hours, ×3 +5 more

Supports a between-group comparison across 39 samples.

How we read this: 13 replicated groups read from 39 sample titles; they account for 39 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
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