title: A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5' exonucleolytic degradation.
abstract: The removal of the mRNA 5' cap structure by the decapping enzyme DCP2 leads to rapid 5'→3' mRNA degradation by XRN1, suggesting that the two processes are coordinated, but the coupling mechanism is unknown. DCP2 associates with the decapping activators EDC4 and DCP1. Here we show that XRN1 directly interacts with EDC4 and DCP1 in human and Drosophila melanogaster cells, respectively. In D. melanogaster cells, this interaction is mediated by the DCP1 EVH1 domain and a DCP1-binding motif (DBM) in the XRN1 C-terminal region. The NMR structure of the DCP1 EVH1 domain bound to the DBM reveals that the peptide docks at a conserved aromatic cleft, which is used by EVH1 domains to recognize proline-rich ligands. Our findings reveal a role for XRN1 in decapping and provide a molecular basis for the coupling of decapping to 5'→3' mRNA degradation.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Joerg E
authors.initials: JE
authors.lastname: Braun
authors.forename: Vincent
authors.initials: V
authors.lastname: Truffault
authors.forename: Andreas
authors.initials: A
authors.lastname: Boland
authors.forename: Eric
authors.initials: E
authors.lastname: Huntzinger
authors.forename: Chung-Te
authors.initials: CT
authors.lastname: Chang
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Haas
authors.forename: Oliver
authors.initials: O
authors.lastname: Weichenrieder
authors.forename: Murray
authors.initials: M
authors.lastname: Coles
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004331:Drosophila melanogaster; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D005095:Exoribonucleases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D059748:Proteolysis; D012333:RNA, Messenger / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D005095:Exoribonucleases; C470512:XRN1 protein, human; D010450:Endopeptidases; C020071:dipeptidyl carboxypeptidase