title: CK2-mediated TEL2 phosphorylation augments nonsense-mediated mRNA decay (NMD) by increase of SMG1 stability.
abstract: Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism that degrades a premature-termination codon (PTC)-containing mRNA. During mammalian NMD, SMG1 and UPF1, key proteins in NMD, join at a PTC and form an SMG1-UPF1-eRF1-eRF3 (SURF) complex by binding UPF1 to eRF3 after PTC-recognition by the translating ribosome. Subsequently, UPF1 is phosphorylated after UPF1-SMG1 moves onto the downstream exon junction complex (EJC). However, the cellular events that induce UPF1 and SMG1 complex formation and increase NMD efficiency before PTC recognition remain unclear. Here, we show that telomere-maintenance 2 (TEL2) phosphorylation by casein-kinase 2 (CK2) increases SMG1 stability, which increases UPF1 phosphorylation and, ultimately, augments NMD. Inhibition of CK2 activity or downregulation of TEL2 impairs NMD. Intriguingly, loss of TEL2 phosphorylation reduces UPF1-bound PTC-containing mRNA and the formation of the SMG1-UPF1 complex. Thus, our results identify a new function of CK2-mediated TEL2 phosphorylation in a mammalian NMD.
authors.affiliation: Graduate School for Biomedical Science and Engineering, Hanyang University, Seoul 133-791, South Korea.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Ahn
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jungwook
authors.initials: J
authors.lastname: Hwang
mesh_terms: D015153:Blotting, Western; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018389:Codon, Nonsense / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D059365:Nonsense Mediated mRNA Decay / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D050783:Proto-Oncogene Proteins c-ets / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047390:Casein Kinase II; D018389:Codon, Nonsense; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D050783:Proto-Oncogene Proteins c-ets; D020365:RNA Helicases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; C409823:ETV7 protein, human; C514704:SMG1 protein, human; C101828:UPF1 protein, human
keywords: CK2; NMD; SMG1; TEL2 phosphorylation; UPF1; mRNP remodeling