Hana Cho¹, Kyoung Mi Kim¹, Sisu Han¹, Junho Choe¹, Seung Gu Park², Sun Shim Choi², Yoon Ki Kim^1,*

¹ School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea
² Department of Medical Biotechnology, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea

^*Corresponding author :  Yoon Ki Kim

Summary
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.