title: The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body formation.
abstract: The exon-junction complex (EJC) deposited on a newly spliced mRNA plays an important role in subsequent mRNA metabolic events. Here we show that an EJC core heterodimer, Y14/Magoh, specifically associates with mRNA-degradation factors, including the mRNA-decapping complex and exoribonucleases, whereas another core factor, eIF4AIII/MLN51, does not. We also demonstrate that Y14 interacts directly with the decapping factor Dcp2 and the 5' cap structure of mRNAs via different but overlapping domains and that Y14 inhibits the mRNA-decapping activity of Dcp2 in vitro. Accordingly, overexpression of Y14 prolongs the half-life of a reporter mRNA. Therefore Y14 may function independently of the EJC in preventing mRNA decapping and decay. Furthermore, we observe that depletion of Y14 disrupts the formation of processing bodies, whereas overexpression of a phosphomimetic Y14 considerably increases the number of processing bodies, perhaps by sequestering the mRNA-degradation factors. In conclusion, this report provides unprecedented evidence for a role of Y14 in regulating mRNA degradation and processing body formation and reinforces the influence of phosphorylation of Y14 on its activity in postsplicing mRNA metabolism.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Chuang
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.forename: Kuo-Ming
authors.initials: KM
authors.lastname: Lee
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
mesh_terms: D001665:Binding Sites / Q000235:genetics; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C459802:CASC3 protein, human; C491494:MAGOH protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C406243:RBM8A protein, human; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D039601:Eukaryotic Initiation Factor-4A; D004722:Endoribonucleases; C467723:DCP2 protein, human