title: DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa.
abstract: DCP1 stimulates the decapping enzyme DCP2, which removes the mRNA 5' cap structure committing mRNAs to degradation. In multicellular eukaryotes, DCP1-DCP2 interaction is stabilized by additional proteins, including EDC4. However, most information on DCP2 activation stems from studies in S. cerevisiae, which lacks EDC4. Furthermore, DCP1 orthologs from multicellular eukaryotes have a C-terminal extension, absent in fungi. Here, we show that in metazoa, a conserved DCP1 C-terminal domain drives DCP1 trimerization. Crystal structures of the DCP1-trimerization domain reveal an antiparallel assembly comprised of three kinked alpha-helices. Trimerization is required for DCP1 to be incorporated into active decapping complexes and for efficient mRNA decapping in vivo. Our results reveal an unexpected connectivity and complexity of the mRNA decapping network in multicellular eukaryotes, which likely enhances opportunities for regulating mRNA degradation.
authors: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
authors: Felix
authors: F
authors: Tritschler
authors: Joerg E
authors: JE
authors: Braun
authors: Carina
authors: C
authors: Motz
authors: Catia
authors: C
authors: Igreja
authors: Gabrielle
authors: G
authors: Haas
authors: Vincent
authors: V
authors: Truffault
authors: Elisa
authors: E
authors: Izaurralde
authors: Oliver
authors: O
authors: Weichenrieder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism*; D020169:Caspases; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012315:RNA Caps; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D029721:Drosophila Proteins; D012315:RNA Caps; D015534:Trans-Activators; D004722:Endoribonucleases; C466279:DCP1A protein, human; D020169:Caspases; C103568:Dcp-1 protein, Drosophila