PXD036976 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice |
Description | RNA alternative splicing (AS) expands the regulatory potential of eukaryotic genomes. The mechanisms regulating liver-specific AS profiles and their contribution to liver function are poorly understood. Here, we identify a key role for the splicing factor RNA-binding Fox protein-2 (RBFOX2) in maintaining cholesterol homeostasis in an obesogenic environment in the liver. Using enhanced individual-nucleotide resolution UV-crosslinking and immunoprecipitation (eiCLIP), we identify physiologically relevant targets of RBFOX2 in mouse liver, including the scavenger receptor class B type I (Scarb1). RBFOX2 function is decreased in the liver in diet-induced obesity, causing a Scarb1 isoform switch and alteration of hepatocyte lipid homeostasis. Our findings demonstrate that specific AS programmes actively maintain liver physiology, and underlie the lipotoxic effects of obesogenic diets when dysregulated. Splice-switching oligonucleotides targeting this network alleviate obesityinduced inflammation in the liver and promote an anti-atherogenic lipoprotein profile in the blood, underscoring the potential of isoform-specific RNA therapeutics for treating metabolism-associated diseases. |
HostingRepository | PRIDE |
AnnounceDate | 2022-11-28 |
AnnouncementXML | Submission_2022-11-28_02:14:58.065.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | MiguelPrado |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-09-25 14:33:00 | ID requested | |
⏵ 1 | 2022-11-28 02:14:58 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Mouse, cholesterol, liver, splicing |
Contact List
MiguelPrado |
contact affiliation | Harvard Medical School, Boston, USA Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain |
contact email | miguel.prado@ispasturias.es |
lab head | |
MiguelPrado |
contact affiliation | Harvard Medical School |
contact email | miguel_prado@hms.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD036976
- Label: PRIDE project
- Name: Liver RBFOX2 regulates cholesterol homeostasis via Scarb1 alternative splicing in mice