Staufen1-Mediated mRNA Decay Functions in Adipogenesis

被引:95
作者
Cho, Hana [1 ]
Kim, Kyoung Mi [1 ]
Han, Sisu [1 ]
Choe, Junho [1 ]
Park, Seung Gu [2 ,3 ]
Choi, Sun Shim [2 ,3 ]
Kim, Yoon Ki [1 ]
机构
[1] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea
[2] Kangwon Natl Univ, Dept Med Biotechnol, Coll Biomed Sci, Chunchon 200701, South Korea
[3] Kangwon Natl Univ, Inst Biosci & Biotechnol, Chunchon 200701, South Korea
基金
新加坡国家研究基金会;
关键词
ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; DIVERSE CLASSES; P-BODIES; SURVEILLANCE; COMPLEX; BINDING; IDENTIFICATION; PATHWAYS; PROTEIN;
D O I
10.1016/j.molcel.2012.03.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:495 / 506
页数:12
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