Cells hack virus-like protein to communicate

Sara Reardon in Nature:

Untitled The genomes of plants and animals are littered with the remains of viruses that integrated themselves into their DNA hundreds of millions of years ago. Most of these viral remnants are inactive, but the latest research suggests that some evolved into genes that let cells communicate. A pair of papers¹^,² published in Cell on 11 January suggest that the protein encoded by one such gene uses its virus-like structure to shuttle information between cells: a new form of cellular communication that may be key to long-term memory formation and other neurological functions. Two research groups came across the phenomenon independently while studying extracellular vesicles — pieces of cell membranes that pinch off into bubbles and float away from the cells. These vesicles circulate throughout the body, but little is known about their function. The teams, led by neuroscientist Jason Shepherd at the University of Utah in Salt Lake City and cell biologist Vivian Budnik at the University of Massachusetts Medical School in Worcester, looked at mice and flies (Drosophila melanogaster), respectively.

Protective shells

The researchers found that many of the extracellular vesicles released by neurons contain a gene called Arc, which helps neurons to build connections with one another. Mice engineered to lack Arc have problems forming long-term memories, and several human neurological disorders are linked to this gene. When Shepherd and Budnik analysed the genetic sequences of mouse and fly versions of Arc, they found that they were similar to that of a viral gene called gag. Retroviruses such as HIV use the Gag protein to assemble protective shells called capsids that transport the virus’s genetic material between cells during infection. When the researchers looked at the Arc protein under a high-resolution microscope, they found that it formed a similar capsid and carried the genetic instructions, or messenger RNA (mRNA), that encode Arc. The capsid was then wrapped in a piece of the cell membrane and released as an extracellular vesicle. No other non-viral protein has been shown to form capsids and shuttle mRNA between cells. “It’s groundbreaking,” says Clive Bramham, a neuroscientist at the University of Bergen in Norway.

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