School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Mol Cell. 2012 May 25;46(4):495-506. doi: 10.1016/j.molcel.2012.03.009. Epub 2012 Apr 12.
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, Krüppel-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.
双链 RNA 结合蛋白 Staufen1（Stau1）参与多种基因表达途径。在哺乳动物中，Stau1 通过结合靶 mRNA 的 3'非翻译区并募集 Upf1 来引发 mRNA 的快速降解，从而介导 mRNA 衰变（SMD）。然而，Upf1 募集后的事件以及 SMD 的生物学重要性仍不清楚。本研究显示 SMD 涉及 PNRC2、脱帽活性和 5'-3'外切核酸酶活性。特别是，Upf1 作为 PNRC2 和 Stau1 结合的衔接蛋白。在脂肪生成过程中，Stau1 和 PNRC2 的丰度增加，Upf1 发生过度磷酸化，从而增强 SMD 效率。有趣的是，下调 SMD 成分会以一种可通过下调抗脂肪生成因子 Krüppel 样因子 2（KLF2）得到挽救的方式减弱脂肪生成，而 KLF2 的 mRNA 被鉴定为 SMD 的底物。因此，本研究数据确定了 SMD 在脂肪生成中的生物学作用。
