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U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations [RNA-Seq]

GSE328821 Homo sapiens (human) RNA-seq (gene expression) 53 samples Submitted 2026/04/29 Platform GPL24676Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 53 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)
Topic
Lung cancerThis series is part of our curated briefing on it.
Samples
53 samples: 13 conditions, mostly with about 4 replicates eachGroups 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
U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutationsNature genetics · 2026
Summary (written by the submitters)
The mechanisms by which mutations of the splicing factor gene U2AF1 contribute to lung adenocarcinoma pathogenesis are not well understood. Here, we used prime editing to modify the endogenous U2AF1 gene in lung adenocarcinoma cells and assessed the resulting impact on alternative splicing. One specific KRAS mutation, G12S, leads to skipping of KRAS exon 2 and generation of a non-functional KRAS transcript.
Read the full summary ↓
However, expression of the U2AF1 S34F mutant reverts this exon skipping and restores KRAS function, leading to an enrichment of U2AF1 S34F mutations in KRAS G12S-mutant lung adenocarcinomas. A comprehensive analysis of splicing factor/oncogene mutation co-occurrence in cancer genomes also revealed significant co-enrichment of KRAS Q61R and U2AF1 I24T mutations. Experimentally, KRAS Q61R mutation leads to KRAS exon 3 skipping, which in turn can be rescued by the expression of U2AF1 I24T. Our findings provide evidence that splicing factor mutations can rescue splicing defects caused by oncogenic mutations in a dynamic process of cascading selection.
Published in
U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations
Walter DM, Cho K, Sivakumar S et al. · Nature genetics 2026 · PMID 42386932 · doi:10.1038/s41588-026-02648-1
This dataset
Open GSE328821 in finder → Find more human RNA-seq datasets → Lung cancer landscape →
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 GSE328821_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 PRJNA1456598 and SRA study SRP694009. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42386932) ↗
Study design
13 conditions, mostly with about 4 replicates each
A549 Cells, U2AF1 S34F, backedit to wildtype … ×6 NCI-H441 Cells, U2AF1 S34F TTC codon, sample ×6 A549 Cells, U2AF1 S34A, sample ×4 A549 Cells, U2AF1 S34C, sample ×4 A549 Cells, U2AF1 S34F, sample ×4 A549 Cells, Parental, sample ×4 A549 Cells, U2AF1 S34S, sample ×4 A549 Cells, U2AF1 S34Y, sample ×4 +6 more

Supports a between-group comparison across 52 samples.

How we read this: 13 replicated groups read from 53 sample titles; they account for 52 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

+ 13 more — browse all 53 samples with per-sample file links →

More Lung cancer datasets

Search all human RNA-seq datasets in GEO →

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