基础医学与临床 ›› 2025, Vol. 45 ›› Issue (10): 1284-1290.doi: 10.16352/j.issn.1001-6325.2025.10.1284

• 研究论文 • 上一篇    下一篇

急性冷刺激激活小鼠棕色脂肪组织STAU1介导的mRNA降解途径

郭子豪, 万梦瑶, 聂诗琪, 梁小弟*   

  1. 新疆医科大学 基础医学院 生物化学与分子生物学教研室,新疆 乌鲁木齐 830011
  • 收稿日期:2025-04-23 修回日期:2025-07-18 出版日期:2025-10-05 发布日期:2025-09-22
  • 通讯作者: *xiaodiliang@xjmu.edu.cn
  • 基金资助:
    国家自然科学基金(82260177);省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2023-20)

Activation of STAU1-mediated mRNA decay pathway in brown adipose tissue of mice by acute cold stress

GUO Zihao, WAN Mengyao, NIE Shiqi, LIANG Xiaodi*   

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011,China
  • Received:2025-04-23 Revised:2025-07-18 Online:2025-10-05 Published:2025-09-22
  • Contact: *xiaodiliang@xjmu.edu.cn

摘要: 目的 探究急性冷刺激对小鼠棕色脂肪组织STAU1介导的mRNA降解途径(SMD)的影响及下游调控的靶基因。方法 对小鼠进行4 ℃的急性冷刺激(CS),48 h后提取小鼠的棕色脂肪组织检测Stau1、Ucp1及Pparγ等基因的表达,并与室温对照组(RT)小鼠进行比较。对CS组及RT组小鼠的棕色脂肪组织进行转录组学测序,并对测序结果进行差异基因功能富集分析。利用CRISPR-Cas9技术对小鼠棕色脂肪细胞进行Stau1基因的敲除,并分析敲除后产热基因的表达情况。结果 急性冷刺激处理会诱导Stau1基因的表达,并促进SMD途径降解下游靶基因Serpineb1、Klf2及c-Jun的表达(P<0.05)。Stau1敲除后小鼠棕色脂肪细胞的糖脂代谢通路明显上调,产热相关基因Ucp1、Prdm16、ATP5o、Dio2、Pgc1α表达上调(P<0.05)。结论 急性冷刺激会促进小鼠棕色脂肪组织中的SMD途径,而SMD途径在棕色脂肪细胞中主要调控代谢及产热途径。

关键词: 急性冷刺激, 棕色脂肪组织, STAU1, RNA降解途径, 转录组测序

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

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