Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1868, Issue 5, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbalip.2023.159293
Keywords
Staufen1; Adipogenesis; Peroxisome proliferator-activated receptor; gamma; Alternative splicing; RNA sequencing
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This study reveals that STAU1 regulates the alternative splicing of PPAR gamma in adipocyte differentiation by affecting exon skipping. The findings provide insights into the role of STAU1 in adipocyte differentiation and the regulatory network of adipocyte differentiation-related gene expression.
During adipocyte differentiation, specific genes such as peroxisome proliferator-activated receptor gamma (PPAR gamma) are transcribed and post-transcriptional pre-mRNA is processed into mature mRNA. Since Ppar gamma 2 pre-mRNAs contain putative binding sites for STAUFEN1 (STAU1), which can affect the alternative splicing of pre-mRNA, we hypothesized that STAU1 might regulate the alternative splicing of Ppar gamma 2 pre-mRNA. In this study, we found that STAU1 affects the differentiation of 3 T3-L1 pre-adipocytes. Through RNA-seq analysis, we confirmed that STAU1 can regulate alternative splicing events during adipocyte differentiation, mainly through exon skipping, which suggests that STAU1 is mainly involved in exon splicing. In addition, gene annotation and cluster analysis revealed that the genes affected by alternative splicing were enriched in lipid metabolism pathways. We further demonstrated that STAU1 can regulate the alternative splicing of Ppar gamma 2 pre-mRNA and affect the splicing of exon E1 through RNA immuno-precipitation, photoactivatable ribonucleotide enhanced crosslinking and immunoprecipitation, and sucrose density gradient centrifugation assays. Finally, we confirmed that STAU1 can regulate the alternative splicing of Ppar gamma 2 pre-mRNA in stromal vascular fraction cells. In summary, this study improves our understanding of the function of STAU1 in adipocyte differentiation and the regulatory network of adipocyte differentiation-related gene expression.
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