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Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cells.

GSE279274 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2024/11/14 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 16 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
16 samples: 6 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
Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cellsThe Journal of biological chemistry · 2025
Summary (written by the submitters)
Farnesoid X receptor α (FXRα) is a bile acid-activated nuclear receptor that sets the expression of glycolytic and lipogenic target genes by interacting with the 9-cis-retinoic acid receptor α (RXRα). Jointly with recruited cofactors, the current FXRα proteins reported so far in human and rodent have been described to regulate both isoform (α1-4)- and tissue-specific gene expression profiles in order to integrate energy balance and adapt metabolism.
Read the full summary ↓
Here, we studied the biological functions of a FXRα naturally occurring spliced exon 5 isoform (FXRαse5) lacking the second zinc-binding module of the DNA Binding Domain (DBD). We show that the FXRαse5 is expressed in all FXRα-expressing tissues and cells from human and mouse, and that it is not able to either bind to its response element or activate FXRα dependent transcription. In parallel, this spliced variant displayed differential interaction capacities with its obligate heterodimer partner RXRα that may account for silencing of this permissive dimer for signal transduction. Finally, deletion of exon 5 by gene edition in HepG2 cells leads to FXRα loss-of-function, increased expression for LRH1 metabolic sensor and CD36 fatty acid transporter in conjunction with changes in glucose and triglycerides homeostasis. All together, these findings highlighted a novel mechanism by which alternative splicing may regulate FXRα gene function to fine-tune adaptive and/or metabolic responses. Taking this into account could deepen our understanding on how splicing events might hinder FXRα activity to regulate specific transcriptional programs and contribute to modify energy metabolism in normal tissues and metabolic diseases.
Published in
Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cells
Garcia M, Holota H, De Haze A et al. · The Journal of biological chemistry 2025 · PMID 39608717 · doi:10.1016/j.jbc.2024.108022
This dataset
Open GSE279274 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 GSE279274_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 PRJNA1171781 and SRA study SRP537935. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39608717) ↗
Study design
6 conditions, mostly in triplicate
HepG2 cells, FXR1a, 24 hours, ×3 HepG2 cells, FXRDE5, 24 hours, ×3 HepG2 cells, FXR1a, 48 hours, ×3 HepG2 cells, FXRDE5, 48 hours, ×3 HepG2 cells, control, 24hours, ×2 HepG2 cells, control, 48hours, ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 replicated groups read from 16 sample titles; they account for 16 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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