Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator

Cell. 2015 Dec 3;163(6):1468-83. doi: 10.1016/j.cell.2015.11.020.


Memories are thought to be formed in response to transient experiences, in part through changes in local protein synthesis at synapses. In Drosophila, the amyloidogenic (prion-like) state of the RNA binding protein Orb2 has been implicated in long-term memory, but how conformational conversion of Orb2 promotes memory formation is unclear. Combining in vitro and in vivo studies, we find that the monomeric form of Orb2 represses translation and removes mRNA poly(A) tails, while the oligomeric form enhances translation and elongates the poly(A) tails and imparts its translational state to the monomer. The CG13928 protein, which binds only to monomeric Orb2, promotes deadenylation, whereas the putative poly(A) binding protein CG4612 promotes oligomeric Orb2-dependent translation. Our data support a model in which monomeric Orb2 keeps target mRNA in a translationally dormant state and experience-dependent conversion to the amyloidogenic state activates translation, resulting in persistent alteration of synaptic activity and stabilization of memory.

MeSH terms

  • 3' Untranslated Regions
  • Amyloidogenic Proteins / chemistry
  • Amyloidogenic Proteins / metabolism
  • Animals
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Memory, Long-Term*
  • Mice
  • Polyadenylation
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • RNA-Binding Proteins / metabolism
  • Serine Endopeptidases / genetics
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / chemistry
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • 3' Untranslated Regions
  • Amyloidogenic Proteins
  • CPEB protein, mouse
  • Drosophila Proteins
  • Orb2 protein, Drosophila
  • RNA-Binding Proteins
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Serine Endopeptidases
  • Teq protein, Drosophila