Staufen1-Mediated mRNA Decay Functions in Adipogenesis

Hana Cho; Kyoung Mi Kim; Sisu Han; Junho Choe; Seung Gu Park; Sun Shim Choi; Yoon Ki Kim

doi:10.1016/j.molcel.2012.03.009

Staufen1-Mediated mRNA Decay Functions in Adipogenesis

Hana Cho, Kyoung Mi Kim, Sisu Han, Junho Choe, Seung Gu Park, Sun Shim Choi, Yoon Ki Kim

Division of Life Sciences

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	495-506
Number of pages	12
Journal	Molecular Cell
Volume	46
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2012.03.009
Publication status	Published - 2012 May 25

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2012.03.009

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@article{8f48cdf6c22a4ddc9e6697016e41bff1,

title = "Staufen1-Mediated mRNA Decay Functions in Adipogenesis",

abstract = "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, Kr{\"u}ppel-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.",

author = "Hana Cho and Kim, {Kyoung Mi} and Sisu Han and Junho Choe and Park, {Seung Gu} and Choi, {Sun Shim} and Kim, {Yoon Ki}",

note = "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 Ort{\'i}n 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. ",

year = "2012",

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day = "25",

doi = "10.1016/j.molcel.2012.03.009",

language = "English",

volume = "46",

pages = "495--506",

journal = "Molecular Cell",

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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 -

Staufen1-Mediated mRNA Decay Functions in Adipogenesis

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