title: MARVELD1 Inhibits Nonsense-Mediated RNA Decay by Repressing Serine Phosphorylation of UPF1.
abstract: We have observed low expression levels of MARVELD1, a novel tumor repressor, in multiple tumors; however, its function in normal cells has not been explored. We recently reported that MARVELD1 interacts with importin β1, which plays an important role in nonsense-mediated RNA decay(NMD). Here, we demonstrate that MARVELD1 substantially inhibits nonsense-mediated RNA decay by decreasing the pioneer round of translation but not steady-state translation, and we identify MARVELD1 as an important component of the molecular machinery containing UPF1 and Y14. Furthermore, we determined the specific regions of MARVELD1 and UPF1 responsible for their interaction. We also showed that MARVELD1 promotes the dissociation of SMG1 from UPF1, resulting in the repression of serine phosphorylation of UPF1, and subsequently blocks the recruitment of SMG5, which is required for ensuing SMG5-mediated exonucleolytic decay. Our observations provide molecular insight into the potential function of MARVELD1 in nonsense-mediated RNA decay.
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Jianran
authors.initials: J
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Li
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D059365:Nonsense Mediated mRNA Decay / Q000502:physiology*; D010766:Phosphorylation; D000072417:Protein Domains; D020365:RNA Helicases; D020871:RNA Stability; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: C438144:ASI1 protein, S cerevisiae; D002352:Carrier Proteins; C542435:MARVELD1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C406243:RBM8A protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C515801:SMG5 protein, human; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D012694:Serine; D020365:RNA Helicases; C101828:UPF1 protein, human