Abstract: Objective To investigate the effect of acute cold stimulation on the staufen1-mediated mRNA decay(SMD) pathway in brown adipose tissue of mice and the downstream regulated target genes. Methods Mice were subjected to acute cold stimulation (CS) at 4 ℃. After 48 hours, the brown adipose tissue of mice was extracted to detect the expression of genes including as Stau1, Ucp1 and Pparγ, and compared with mice in room temperature control group (RT). Transcriptomic sequencing was performed on the brown adipose tissue of mice in the CS group and in the RT group, and the functional enrichment analysis of differential genes was performed on the sequencing results. The Stau1 gene was knocked out in the brown adipocytes of mice using CRISPR-Cas9 technology, and the expression of thermogenic genes after knockout was analyzed. Results Acute cold stimulation induced the expression of Stau1 gene and promoted the degradation of downstream target genes Serpineb1, Klf2 and c-Jun in the SMD pathway(P＜0.05). After Stau1 knockout, the glycolipid metabolism pathway of brown adipocytes in mice was significantly up-regulated, and the expression of thermogenesis-related genes Ucp1, Prdm16, ATP5o, Dio2 and Pgc1α was up-regulated (P＜0.05). Conclusions Acute cold stimulation promotes the SMD pathway in brown adipose tissue of mice, and SMD pathway mainly regulates the metabolic and thermogenic pathways in brown adipocytes.

Key words: acute cold stimulation, brown adipose tissue, STAU1, RNA degradation pathway, transcriptome sequencing