TY - JOUR
T1 - Staufen1-Mediated mRNA Decay Functions in Adipogenesis
AU - Cho, Hana
AU - Kim, Kyoung Mi
AU - Han, Sisu
AU - Choe, Junho
AU - Park, Seung Gu
AU - Choi, Sun Shim
AU - Kim, Yoon Ki
N1 - Funding Information:
We thank Lynne E. Maquat for providing NMD reporter plasmids and α-Upf1 antibody, Luc DesGroseillers for plasmid expressing Stau1 55 -HA 3 , Jens Lykke-Andersen for plasmid expressing FLAG-Dcp1a, Juan Ortín for anti-human Stau1 antibody, and Young-Gyu Ko and Jeong-Ho Hong for scientific comments. This work was supported by the Korea Healthcare Technology R&D Project (A103001), Ministry for Health, Welfare and Family Affairs, Republic of Korea, and the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea government (MEST) (2009-0078061 and 2009-0084897). H.C., K.M.K., and J.C. were supported in part by a Seoul Science Fellowship. S.H. was supported in part by the project of Global Ph.D. Fellowship, which the National Research Foundation of Korea has conducted since 2011.
PY - 2012/5/25
Y1 - 2012/5/25
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2012.03.009
DO - 10.1016/j.molcel.2012.03.009
M3 - Article
C2 - 22503102
AN - SCOPUS:84861461351
VL - 46
SP - 495
EP - 506
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 4
ER -