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Pan-SNCA vs. isoform-selective antisense oligonucleotide knockdown of SNCA-dIRE in SK-MEL-28 cells (ATF4 follow-up)

GSE342033 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/08/06 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
12 samples: 3 × SK-MEL-28, 2 uM ASO2 (NTC), biol vs 3 × SK-MEL-28, 2 uM ASO3 (pan-SNCA), biol vs 3 × SK-MEL-28, 2 uM ASO43 (dIRE), biol vs 3 × SK-MEL-28, 2 uM ASO550 (dIRE), biolGroups 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.
Summary (written by the submitters)
Parkinson's disease is a progressive neurodegenerative disorder often characterized by the accumulation of misfolded alpha-synuclein protein (aSyn) in the brain. While rare genetic variants in SNCA can cause neuronal aSyn accumulation and neurodegeneration in some cases of familial disease, the molecular mechanisms driving SNCA associated risk in idiopathic Parkinson's disease remain elusive.
Read the full summary ↓
The canonical SNCA mRNA transcript contains a 5'UTR iron response element (IRE) that regulates translation based on cellular iron content. In this study we investigate an alternative transcript isoform lacking this element (dIRE) by evaluating SNCA transcript profiles across neuronal cell lines and post-mortem brain datasets. We show evidence that elevated dIRE expression correlates with increased disease risk in genome-wide association studies and is preferentially expressed in dopaminergic cells. Further, we show that dIRE expression may depend on transcription start site selection controlled by CpG methylation overlapping a known transcription factor binding site, where a PD associated risk haplotype exhibits lower methylation of this CpG site. To probe isoform function, we design and test isoform-specific antisense oligonucleotides (ASOs). With these ASO tools we demonstrate that the protective IRE isoform uniquely suppresses ATF4, an integrated stress response marker elevated in the substantia nigra of post-mortem Parkinson's disease brains. These analyses suggest that uncoupling aSyn translation from intracellular iron concentration may drive neurodegeneration in idiopathic Parkinson's disease. Importantly, non-isoform-selective SNCA-lowering strategies may trigger stress pathways and worsen disease progression, establishing isoform-specific ASOs as key stepping stones toward design of precision therapeutics for Parkinson's disease.
This dataset
Open GSE342033 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 GSE342033_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 PRJNA1505207 and SRA study SRP723042. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × SK-MEL-28, 2 uM ASO2 (NTC), biol vs 3 × SK-MEL-28, 2 uM ASO3 (pan-SNCA), biol vs 3 × SK-MEL-28, 2 uM ASO43 (dIRE), biol vs 3 × SK-MEL-28, 2 uM ASO550 (dIRE), biol

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
Datasets on a similar topic

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