Staufen1-Mediated mRNA Decay Functions in Adipogenesis
Staufen1-Mediated mRNA Decay Functions in Adipogenesis
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DOI：
10.1016/j.molcel.2012.03.009
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发表时间：
2012-05-25
期刊：
影响因子：
16
通讯作者：
Kim, Yoon Ki
中科院分区：
文献类型：
--
作者：
Cho, Hana;Kim, Kyoung Mi;Kim, Yoon Ki
双链RNA结合蛋白Staufen 1（Stau 1）参与多种基因表达途径。对于哺乳动物中的Stau 1介导的mRNA降解（SMD），Stau 1结合靶mRNA的3'非翻译区并募集Upf 1以引起快速mRNA降解。然而，Upf 1募集下游的事件和SMD的生物学重要性仍不清楚。在这里，我们表明，SMD涉及PNRC 2，脱帽活性，和5 '-至-3'外切核酸酶活性。特别是，Upf 1作为一个衔接蛋白的协会PNRC 2和Stau 1。在脂肪形成过程中，Stau 1和PNRC 2的丰度增加，Upf 1变得过度磷酸化，因此SMD效率提高。有趣的是，SMD组分的下调以通过抗脂肪形成因子Kruppel样因子2（KLF 2）的下调来拯救的方式减弱脂肪形成，Kruppel样因子2（KLF 2）的mRNA被鉴定为SMD的底物。因此，我们的数据确定了SMD在脂肪形成中的生物学作用。
The double-stranded RNA binding protein Staufen1 (Stau1) is involved in diverse gene expression pathways. For Stau1-mediated mRNA decay (SMD) in mammals, Stau1 binds to the 3' untranslated region of target mRNA and recruits Upf1 to elicit rapid mRNA degradation. However, the events downstream of Upf1 recruitment and the biological importance of SMD remain unclear. Here we show that SMD involves PNRC2, decapping activity, and 5'-to-3' exonucleolytic activity. In particular, Upf1 serves as an adaptor protein for the association of PNRC2 and Stau1. During adipogenesis, Stau1 and PNRC2 increase in abundance, Upf1 becomes hyperphosphorylated, and consequently SMD efficiency is enhanced. Intriguingly, downregulation of SMD components attenuates adipogenesis in a way that is rescued by downregulation of an antiadipogenic factor, Kruppel-like factor 2 (KLF2), the mRNA of which is identified as a substrate of SMD. Our data thus identify a biological role for SMD in adipogenesis.