title: Insulin Signaling Augments eIF4E-Dependent Nonsense-Mediated mRNA Decay in Mammalian Cells.
abstract: Nonsense-mediated mRNA decay (NMD) modulates the level of mRNA harboring a premature termination codon (PTC) in a translation-dependent manner. Inhibition of translation is known to impair NMD; however, few studies have investigated the correlation between enhanced translation and increased NMD. Here, we demonstrate that insulin signaling events increase translation, leading to an increase in NMD of eIF4E-bound transcripts. We provide evidence that (i) insulin-mediated enhancement of translation augments NMD and rapamycin abrogates this enhancement; (ii) an increase in AKT phosphorylation due to inhibition of PTEN facilitates NMD; (iii) insulin stimulation increases the binding of up-frameshift factor 1 (UPF1), most likely to eIF4E-bound PTC-containing transcripts; and (iv) insulin stimulation induces the colocalization of UPF1 and eIF4E in processing bodies. These results illustrate how extracellular signaling promotes the removal of eIF4E-bound NMD targets.
authors.affiliation: Graduate School for Biomedical Science & Engineering, FTC1202-8, Hanyang University, 222 Wangimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
authors.forename: Jungyun
authors.initials: J
authors.lastname: Park
authors.affiliation: Graduate School for Biomedical Science & Engineering, FTC1202-8, Hanyang University, 222 Wangimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
authors.forename: Aravinth K
authors.initials: AK
authors.lastname: Jayabalan
authors.affiliation: Department of Cellular and Molecular Medicine, College of Medicine, Chosun University, Gwangju, Republic of Korea.
authors.forename: Takbum
authors.initials: T
authors.lastname: Ohn
authors.affiliation: Department of Pharmacology, College of Medicine, Hanyang University, 222 Wangimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. Electronic address: hckoh@hanyang.ac.kr.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Koh
authors.affiliation: Graduate School for Biomedical Science & Engineering, FTC1202-8, Hanyang University, 222 Wangimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; Department of Medical Genetics, College of Medicine, FTC1202-8, Hanyang University, 222 Wangimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. Electronic address: jwhwang@hanyang.ac.kr.
authors.forename: Jungwook
authors.initials: J
authors.lastname: Hwang
mesh_terms: D000818:Animals; D039561:Eukaryotic Initiation Factor-4E / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D059365:Nonsense Mediated mRNA Decay / Q000187:drug effects*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D020123:Sirolimus
keywords: Insulin; NMD; PI3K/AKT/mTOR; Processing body; Translation