title: SMG1 regulates adipogenesis via targeting of staufen1-mediated mRNA decay.
abstract: Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.
authors.affiliation: Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.forename: Sisu
authors.initials: S
authors.lastname: Han
authors.forename: Ok Hyun
authors.initials: OH
authors.lastname: Park
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004722:Endoribonucleases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D020365:RNA Helicases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C492185:STAU1 protein, human; C514704:SMG1 protein, human; C466279:DCP1A protein, human; C101828:UPF1 protein, human
keywords: Adipogenesis; Nonsense-mediated mRNA decay; SMG1; Stau1-mediated mRNA decay; Staufen1; Upf1