RGD Reference Report - The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. - Rat Genome Database

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The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer.

Authors: Pastuzyn, Elissa D  Day, Cameron E  Kearns, Rachel B  Kyrke-Smith, Madeleine  Taibi, Andrew V  McCormick, John  Yoder, Nathan  Belnap, David M  Erlendsson, Simon  Morado, Dustin R  Briggs, John A G  Feschotte, Cédric  Shepherd, Jason D 
Citation: Pastuzyn ED, etal., Cell. 2018 Jan 11;172(1-2):275-288.e18. doi: 10.1016/j.cell.2017.12.024.
RGD ID: 13514080
Pubmed: PMID:29328916   (View Abstract at PubMed)
PMCID: PMC5884693   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2017.12.024   (Journal Full-text)

The neuronal gene Arc is essential for long-lasting information storage in the mammalian brain, mediates various forms of synaptic plasticity, and has been implicated in neurodevelopmental disorders. However, little is known about Arc's molecular function and evolutionary origins. Here, we show that Arc self-assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is released from neurons in extracellular vesicles that mediate the transfer of Arc mRNA into new target cells, where it can undergo activity-dependent translation. Purified Arc capsids are endocytosed and are able to transfer Arc mRNA into the cytoplasm of neurons. These results show that Arc exhibits similar molecular properties to retroviral Gag proteins. Evolutionary analysis indicates that Arc is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are also ancestors to retroviruses. These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ArcRatmRNA transport involved_inIDA PMID:29328916UniProt 
ArcRatprotein homooligomerization involved_inIDA PMID:29328916UniProt 
ArcRatvesicle-mediated intercellular transport involved_inIDA PMID:29328916UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ArcRatextracellular vesicle located_inIDA PMID:29328916UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ArcRatmRNA binding enablesIDA PMID:29328916UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Arc  (activity-regulated cytoskeleton-associated protein)


Additional Information