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

The story so far…

Retroviruses (e.g HIV) reproduce by entering target cells and inducing the target cell to translate the viral DNA to form new baby viruses.

Meanwhile…

The Arc gene is known to be partially responsible for neuroplasticity and memory formation in human brains, and mutations to this gene can possibly result in neurodevelopmental disorders. But for years it has been unclear what Arc is really doing.

Until one day…

Pastuzyn et al explored the role of endogenous Arc proteins and found that it appears that Arc is structurally similar to retroviral, “virus-like” proteins: In fact, Arc proteins appear to be able to form capsids — mini-capsules of proteins that enable Arc to transit across the cellular membrane of neurons. These structures look super similar to retroviral capsid functional domains, which suggests that Arc arrived in the human genome as a result of viral infection.

Meanwhile: The big take-home lesson of this paper is that RNA is a required component in this Arc capsid-based export process. So we know three things: Arc forms capsids; RNA exists inside of those capsids; these capsids are absorbed by neighboring cells.

From this, we learn a surprising fact about the nervous system: Apparently, CNS cells are able to “donate” mRNA stretches to other cells in the vicinity.

This is extremely interesting, but also perhaps unsurprising: If cells can receive mRNA from their neighbors, it’s a good way to exchange information about the surrounding environment, or to receive feedback even if there is no direct synapse to allow the two neurons to communicate electrochemically.