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Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer

GSE276695 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2024/12/27 Platform GPL24676Platform GPL16791Platform GPL21697
At a glance

RNA-seq (gene expression) · human · 24 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
24 samples: 11 conditions, mostly in duplicateGroups 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
Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancerNucleic acids research · 2024
Summary (written by the submitters)
Messenger RNA (mRNA) translation is a tightly controlled process frequently deregulated in cancer. Key to this deregulation are transfer RNAs (tRNAs), whose expression, processing, and post-transcriptional modifications are often altered in cancer to support cellular transformation. In conditions of limiting levels of amino acids, this deregulated control of protein synthesis leads to aberrant protein production in the form of ribosomal frameshifting or misincorporation of non-cognate amino acids.
Read the full summary ↓
Here, we studied leucine, an essential amino acid coded for in mRNA by six different codons. Surprisingly, we found that leucine deprivation leads to ribosomal stalling and aberrant protein production in various cancer cell types, predominantly at one codon, UUA. Similar effects were observed after treatment with chemotherapeutic agents, implying a shared mechanism controlling the downstream effects on mRNA translation. In both conditions, a limitation in the availability of tRNALeu(UAA) for protein production was shown to be the cause for this dominant effect on UUA codons. The induced aberrant proteins can be processed and immune-presented as neoepitopes, and can direct T-cell killing. Altogether, we uncovered a novel mode of interplay between DNA damage, regulation of tRNA availability for mRNA translation, and aberrant protein production in cancer that could be exploited for anti-cancer therapy.
Published in
Chemotherapeutic agents and leucine deprivation induce codon-biased aberrant protein production in cancer
Kochavi A, Nagel R, Körner PR et al. · Nucleic acids research 2024 · PMID 39588782 · doi:10.1093/nar/gkae1110
This dataset
Open GSE276695 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 GSE276695_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 PRJNA1158720 and SRA study SRP531679. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39588782) ↗
Study design
11 conditions, mostly in duplicate
PC3_WT ×2 PC3_Leucine_depletion ×2 PC3_Etoposide ×2 MDA-MB-231_WT ×2 MDA-MB-231_Leucine_depletion ×2 MDA-MB-231_tRNA_TAA_overexpression_WT ×2 MDA-MB-231_tRNA_TAA_overexpression_Leu_deplet… ×2 MDA-MB-231_tRNA_CAA_overexpression_WT ×2 +5 more

Supports a case/control comparison: 8 samples read as cases, 2 as controls.

How we read this: 11 replicated groups read from 24 sample titles; they account for 22 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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