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

TY - JOUR

T1 - The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer

AU - Pastuzyn, Elissa D.

AU - Day, Cameron E.

AU - Kearns, Rachel B.

AU - Kyrke-Smith, Madeleine

AU - Taibi, Andrew V.

AU - McCormick, John

AU - Yoder, Nathan

AU - Belnap, David M.

AU - Erlendsson, Simon

AU - Morado, Dustin R.

AU - Briggs, John A. G.

AU - Feschotte, Cédric

AU - Shepherd, Jason D.

N1 - Correction to: The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer

PY - 2018/1/11

Y1 - 2018/1/11

N2 - 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. The neuronal protein Arc is evolutionarily related to retrotransposon Gag proteins and forms virus-like capsid structures that can transfer mRNA between cells in the nervous system.

AB - 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. The neuronal protein Arc is evolutionarily related to retrotransposon Gag proteins and forms virus-like capsid structures that can transfer mRNA between cells in the nervous system.

U2 - 10.1016/j.cell.2017.12.024

DO - 10.1016/j.cell.2017.12.024

M3 - Journal article

C2 - 29328916

SN - 0092-8674

VL - 172

SP - 275-288, E18

JO - Cell

JF - Cell

IS - 1-2

ER -