Omics · study · 2026
Stabilization of insulin receptor mRNA by Star-PAP in metabolic homeostasis [ATAC-seq]
Listed in NCBI GEO
Conserved polyadenylation by poly(A) polymerases (PAPs) is essential for mRNA stability, yet its metabolic functions remain unclear.
Description
Here we identify a rare variant p.D469N (Asp469Asn) in Star-PAP present in lean individuals but absent in obese cases. Adipose-specific Star-PAP knockout mice develop progressive adipose tissue loss, hepatic steatosis, and severe insulin resistance, phenocopying human lipodystrophy.
Mechanistically, Star-PAP directly binds the the insulin receptor (InsR) mRNA 3’–UTR to stabilize its transcript. Both deletion of Star-PAP and p.D469N variant decrease InsR mRNA maturation. Star-PAP deficiency impaires insulin receptor signaling and adipocyte lipid storage, while restoring InsR in adipocytes partially ameliorates the lipodystrophic phenotypes.
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Notably, Star-PAP deficiency disruptes acetyl-CoA homeostasis secondary to insulin signaling defects, accompanied by reduced histone acetylation at fatty acid synthesis genes. Pyruvate supplementation effectively restores acetyl-CoA levels and histone acetylation, thereby rescuing the gene expression and lipogenesis. Together, our results identify Star-PAP-mediated RNA polyadenylation as a mechanism governing adipose homeostasis, positioning Star-PAP as a key regulator of insulin receptor signaling and lipodystrophy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345555 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345555 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1521294 ncbi.nlm.nih.gov/bioproject/PRJNA1521294 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE345555 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |