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, 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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Sisu
authors.initials: S
authors.lastname: Han
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.forename: Seung Gu
authors.initials: SG
authors.lastname: Park
authors.forename: Sun Shim
authors.initials: SS
authors.lastname: Choi
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D020365:RNA Helicases; D020871:RNA Stability / Q000235:genetics* / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; C437718:PNRC2 protein, human; C506876:PNRC2 protein, mouse; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C484446:Rent1 protein, mouse; C492185:STAU1 protein, human; C492187:Stau1 protein, mouse; D015534:Trans-Activators; D020365:RNA Helicases; C101828:UPF1 protein, human