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

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    Authors
    Ashley, James A.
    Cordy, Benjamin
    Lucia, Diandra
    Fradkin, Lee G.
    Budnik, Vivian
    Thomson, Travis
    Student Authors
    James Ashley
    Academic Program
    Neuroscience
    UMass Chan Affiliations
    Budnik Lab
    Neurobiology
    Document Type
    Journal Article
    Publication Date
    2018-01-11
    Keywords
    Arc/Arg3.1
    Gag domain
    RNA trafficking
    RNA-binding protein
    exosomes
    extracellular vesicles
    plasticity
    retrotransposon
    synapse
    trans-synaptic RNA transport
    Neuroscience and Neurobiology
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    Link to Full Text
    https://doi.org/10.1016/j.cell.2017.12.022
    Abstract
    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.
    Source
    Cell. 2018 Jan 11;172(1-2):262-274.e11. doi: 10.1016/j.cell.2017.12.022. Link to article on publisher's website
    DOI
    10.1016/j.cell.2017.12.022
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/37944
    PubMed ID
    29328915
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    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cell.2017.12.022
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