{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345396/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345396"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Stabilization of insulin receptor mRNA by Star-PAP in metabolic homeostasis","description":"Conserved polyadenylation by poly(A) polymerases (PAPs) is essential for mRNA stability, yet its metabolic functions remain unclear. 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. 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.","dates":{"publication":"2026/09/08"},"accession":"GSE345396","cross_references":{"GSM":["GSM10002670","GSM10002665","GSM10002664","GSM10002663","GSM10002669","GSM10002668","GSM10002667","GSM10002666"],"GPL":["24247"],"GSE":["345396"],"taxon":["Mus musculus"]}}