Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes

EMBO J. 2018 Apr 3;37(7):e97869. doi: 10.15252/embj.201797869. Epub 2018 Mar 6.


The LSM domain-containing protein LSM14/Rap55 plays a role in mRNA decapping, translational repression, and RNA granule (P-body) assembly. How LSM14 interacts with the mRNA silencing machinery, including the eIF4E-binding protein 4E-T and the DEAD-box helicase DDX6, is poorly understood. Here we report the crystal structure of the LSM domain of LSM14 bound to a highly conserved C-terminal fragment of 4E-T. The 4E-T C-terminus forms a bi-partite motif that wraps around the N-terminal LSM domain of LSM14. We also determined the crystal structure of LSM14 bound to the C-terminal RecA-like domain of DDX6. LSM14 binds DDX6 via a unique non-contiguous motif with distinct directionality as compared to other DDX6-interacting proteins. Together with mutational and proteomic studies, the LSM14-DDX6 structure reveals that LSM14 has adopted a divergent mode of binding DDX6 in order to support the formation of mRNA silencing complexes and P-body assembly.

Keywords: P‐bodies; SLIMs; mRNA decapping; protein–protein interaction networks; translational repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caenorhabditis elegans
  • Crystallography, X-Ray
  • DEAD-box RNA Helicases / chemistry*
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Drosophila melanogaster
  • Eukaryotic Initiation Factor-4E / metabolism
  • HeLa Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs*
  • Protein Structure, Secondary
  • Proteins / chemistry
  • Proteins / metabolism
  • Proteomics
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference / physiology*
  • RNA, Messenger / metabolism*
  • Rec A Recombinases / chemistry
  • Recombinant Proteins / chemistry
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Sequence Alignment


  • EDC4 protein, human
  • Eukaryotic Initiation Factor-4E
  • Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA-associated protein 55, human
  • Recombinant Proteins
  • Ribonucleoproteins
  • Rec A Recombinases
  • DDX6 protein, human
  • DEAD-box RNA Helicases