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Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons

GSE223117 Homo sapiens (human) RNA-seq (gene expression) 29 samples Submitted 2024/06/12 Platform GPL24676Platform GPL20795Platform GPL23702
At a glance

RNA-seq (gene expression) · human · 29 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
29 samples: 9 conditions, mostly in triplicateGroups 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
Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exonsNucleic acids research · 2024
Summary (written by the submitters)
Alternative splicing (AS) generates large amounts of RNA isoforms and dramatically increases the complexities of transcriptomes and proteomes. However, it remains unclear how RNA structures contribute to AS regulation. Here, we systematically search transcriptomes for secondary structures with concealed branch-sites (BSs) in the alternatively spliced introns and predict thousands from six organisms, of which many are evolutionarily conserved.
Read the full summary ↓
Intriguingly, a highly conserved stem-loop structure with concealed BSs is found in animal SF3B3 genes and colocalizes with a downstream poison exon (PE). Destabilization of this structure allows increased usage of the branch sites and results in enhanced PE inclusion in both human and Drosophila cells, leading to decreased expression of SF3B3. Through an RNAi screen of 28 RNA-binding proteins, we find that this stem-loop structure is sensitive to U2 and U2-associated proteins. Furthermore, we find that SF3B3 also facilitates DNA repair and protects genome stability by enhancing interaction between ERCC6/CSB and arrested RNA polymerase II. Importantly, both Drosophila and human cells with the secondary structure mutated by genome editing exhibit altered DNA repair in vivo. This study provides a novel and common mechanism for AS regulation of PEs and reveals a physiological function of SF3B3 in DNA repair.
Published in
Conserved intronic secondary structures with concealed branch sites regulate alternative splicing of poison exons
Li H, Ding Z, Fang ZY et al. · Nucleic acids research 2024 · PMID 38499485 · doi:10.1093/nar/gkae185
This dataset
Open GSE223117 in finder → Find more 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 GSE223117_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 PRJNA925017 and SRA study SRP418026. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38499485) ↗
Study design
9 conditions, mostly in triplicate
Posion exon exclusion in female fly, repeat ×3 Wild Type female fly, repeat ×3 Posion exon exclusion in male fly, repeat ×3 Wild Type male fly, repeat ×3 blank vector, repeat ×3 SF3B4 overexpression, repeat ×3 SF3B3 overexpression, repeat ×3 WT ×3 +3 more

Supports a case/control comparison: 7 samples read as cases, 9 as controls.

How we read this: 9 replicated groups read from 29 sample titles; they account for 27 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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