STAU1 fine-tunes adipose thermogenesis by regulating Ucp1 mRNA stability

Abstract STAU1, an RNA-binding protein central to the STAU1-mediated mRNA decay (SMD) pathway, promotes adipogenesis. This study reveals that STAU1 protein levels positively correlate with obesity severity. Adipose specific STAU1 deficient mice on a high-fat diet showed reduced weight, enhanced thermogenesis, and improved glucose tolerance. Deleting Stau1 gene in brown adipose tissue upregulated UCP1 protein. We further identified that STAU1 binds to the 3′ UTR of Ucp1 mRNA. The β₃ adrenergic receptor pathway enhances SMD activity, while inhibiting the cAMP-PKA pathway downregulates STAU1. Our findings establish STAU1 as a modulatory factor that adjusts thermogenic output in response to diverse thermogenic stimuli, providing insight into post-transcriptional regulation of energy balance and potential therapeutic targets for metabolic disease.