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Auxin-induced depletion of human CCR4-NOT subunits reveals opposing functions of CNOT1 and CNOT4 in mRNA metabolism

GSE277237 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2025/10/23 Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 48 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
48 samples: 48 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
Auxin-induced depletion of human CCR4-NOT subunits reveals opposing functions of CNOT1 and CNOT4 in mRNA metabolismThe Journal of biological chemistry · 2025
Summary (written by the submitters)
CCR4-NOT regulates multiple steps in gene regulation, including transcription, mRNA decay, protein ubiquitylation, and translation. Originally discovered in yeast, this complex is highly conserved across eukaryotes, although its composition and functions differ between mammals and yeast. For example, unlike yeast Not4, human CNOT4 (E3 Ubiquitin Ligase) does not form a stable complex with CCR4-NOT, and its functions are less clear compared to its yeast counterpart.
Read the full summary ↓
To investigate the roles of CNOT1 (the central scaffold subunit) and CNOT4, we developed a rapid auxin-induced degron cell culture system that allows for the acute depletion of these proteins. We studied the effects of their absence on complex integrity, cell growth, and mRNA expression and turnover. Our transcriptome-wide analysis revealed that depleting CNOT1 altered the expression of thousands of transcripts, with the majority showing increased abundance and a general decrease in mRNA decay. Although CNOT4 does not associate with the complex through standard biochemical methods, BioID proximity labelling confirmed its association with the complex in cells. However, depleting CNOT4 did not affect the integrity of CCR4-NOT. In contrast to the effects observed with CNOT1 depletion, reducing CNOT4 levels led to only modest changes in RNA steady-state levels and unexpectedly accelerated global mRNA decay. Finally, we show that the changes in mRNA stability in CCR4-NOT-depleted cells correlated with the codon optimality of the transcripts. Our data suggest that CNOT4 exerts opposite effects on mRNA metabolism compared to CNOT1, and that CNOT4 may have functions distinct from those of complex subunits that promote mRNA degradation.
Published in
Auxin-induced depletion of human CCR4-NOT subunits reveals opposing functions of CNOT1 and CNOT4 in mRNA metabolism
Kulkarni S, Smith C, Akinniyi OT et al. · The Journal of biological chemistry 2025 · PMID 41161383 · doi:10.1016/j.jbc.2025.110862
This dataset
Open GSE277237 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 GSE277237_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 PRJNA1161412 and SRA study SRP532818. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41161383) ↗
Study design
48 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 8 samples read as cases, 8 as controls.

How we read this: Read from 48 sample titles: 48 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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