GEO series

Ectopic expression of cytosolic DHODH uncouples de novo pyrimidine biosynthesis from mitochondrial electron transport

GSE314127 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2025/12/18 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 16 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: 16 samples: 4 × CONTROL vs 4 × INHIBITO vs 4 × SCURA vs 4 × SCURINHGroups 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: Ectopic expression of cytosolic DHODH uncouples de novo pyrimidine biosynthesis from mitochondrial electron transportNature metabolism · 2026

Summary (written by the submitters)

Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme of de novo pyrimidine synthesis. In most eukaryotes, this enzyme is bound to the inner mitochondrial membrane, where it couples orotate synthesis to ubiquinone reduction. As ubiquinone must be regenerated by respiratory complex III, pyrimidine biosynthesis and cellular respiration are tightly coupled.

Read the full summary ↓

Consequently, inhibition of respiration suppresses DNA synthesis and cell proliferation. Here, we show that expression of Saccharomyces cerevisiae URA1 gene (ScURA) in mammalian cells uncouples pyrimidine biosynthesis from mitochondrial electron transport. ScURA forms a homodimer in the cytosol that uses fumarate as electron acceptor instead of ubiquinone, enabling respiration-independent pyrimidine biosynthesis. Cells expressing ScURA are resistant to drugs that inhibit complex III and the mitochondrial ribosome. Additionally, ScURA enables the growth of mtDNA-lacking ρ0 cells in uridine-deficient medium and ameliorates the phenotype of cellular models of mitochondrial diseases. Overall, this genetic tool uncovers the contribution of pyrimidine biosynthesis to the phenotypes arising from electron transport chain defects.

Published in

Ectopic expression of cytosolic DHODH uncouples de novo pyrimidine biosynthesis from mitochondrial electron transport

Curtabbi A, Jaroszewicz SN, Sanz-Cortés R et al. · Nature metabolism 2026 · PMID 41703107 · doi:10.1038/s42255-026-01454-7

This dataset

Open GSE314127 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 GSE314127_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 PRJNA1367968 and SRA study SRP647792. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41703107) ↗

Study design

4 × CONTROL vs 4 × INHIBITO vs 4 × SCURA vs 4 × SCURINH

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM9382188 CONTROL_1 CONTROL
GSM9382189 CONTROL_2 CONTROL
GSM9382190 CONTROL_3 CONTROL
GSM9382191 CONTROL_4 CONTROL
GSM9382192 INHIBITOR_1 INHIBITO
GSM9382193 INHIBITOR_2 INHIBITO
GSM9382194 INHIBITOR_3 INHIBITO
GSM9382195 INHIBITOR_4 INHIBITO
GSM9382196 SCURA_1 SCURA
GSM9382197 SCURA_2 SCURA
GSM9382198 SCURA_3 SCURA
GSM9382199 SCURA_4 SCURA
GSM9382200 SCURINH_1 SCURINH
GSM9382201 SCURINH_2 SCURINH
GSM9382202 SCURINH_3 SCURINH
GSM9382203 SCURINH_4 SCURINH

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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.