Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons

Cell. 2018 Jan 11;172(1-2):262-274.e11. doi: 10.1016/j.cell.2017.12.022.


Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles. This loading and transfer depends on the darc1-mRNA 3' untranslated region, which contains retrotransposon-like sequences. Disrupting transfer blocks synaptic plasticity, suggesting that transfer of dArc1 complexed with its mRNA is required for this function. Notably, cultured cells also release extracellular vesicles containing the Gag region of the Copia retrotransposon complexed with its own mRNA. Taken together, our results point to a trans-synaptic mRNA transport mechanism involving retrovirus-like capsids and extracellular vesicles.

Keywords: Arc/Arg3.1; Gag domain; RNA trafficking; RNA-binding protein; exosomes; extracellular vesicles; plasticity; retrotransposon; synapse; trans-synaptic RNA transport.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport
  • Cells, Cultured
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Products, gag / chemistry
  • Gene Products, gag / genetics*
  • Multivesicular Bodies / metabolism*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / metabolism
  • Neuronal Plasticity
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / physiology
  • Protein Binding
  • Protein Domains
  • RNA, Messenger / metabolism*
  • Retroelements / genetics


  • Cytoskeletal Proteins
  • Drosophila Proteins
  • Gene Products, gag
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Retroelements
  • activity regulated cytoskeletal-associated protein
  • Peptide Hydrolases
  • Copia protein, Drosophila