Structural basis of mRNA-cap recognition by Dcp1-Dcp2

Nat Struct Mol Biol. 2016 Nov;23(11):987-994. doi: 10.1038/nsmb.3301. Epub 2016 Oct 3.


Removal of the 5' cap on mRNA by the decapping enzyme Dcp2 is a critical step in 5'-to-3' mRNA decay. Understanding the structural basis of Dcp2 activity has been a challenge because Dcp2 is dynamic and has weak affinity for the cap substrate. Here we present a 2.6-Å-resolution crystal structure of a heterotrimer of fission yeast Dcp2, its essential activator Dcp1, and the human NMD cofactor PNRC2, in complex with a tight-binding cap analog. Cap binding is accompanied by a conformational change in Dcp2, thereby forming a composite nucleotide-binding site comprising conserved residues in the catalytic and regulatory domains. Kinetic analysis of PNRC2 revealed that a conserved short linear motif enhances both substrate affinity and the catalytic step of decapping. These findings explain why Dcp2 requires a conformational change for efficient catalysis and reveals that coactivators promote RNA binding and the catalytic step of decapping, possibly through different conformational states.

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Conserved Sequence
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • RNA Caps / metabolism*
  • RNA Stability
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Schizosaccharomyces / chemistry
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism


  • Dcp1 protein, S pombe
  • Dcp2 protein, S pombe
  • PNRC2 protein, human
  • RNA Caps
  • Receptors, Cytoplasmic and Nuclear
  • Schizosaccharomyces pombe Proteins
  • Trans-Activators