22 January 2018

Viral gene transfer

Two independent groups of scientists from the University of Utah and the University of Massachusetts Medical School have discovered that the Arc gene, which is of great importance for learning, is able to transmit genetic information from one neuron to another in shells similar to the capsids of viruses. In other words, researchers have found a new way for neurons to interact.

It is known that the Arc gene is responsible for the brain's ability to store new information. Previous studies have found similarities between some proteins whose synthesis encodes Arc and proteins of viruses such as HIV.

Researchers at the University of Utah have begun studying the Arc gene by injecting it into bacterial cells. They saw that the protein synthesized by these cells took a form resembling a capsid – the outer shell protecting the genetic information of the virus. The "capsid" was similar to the viral envelope not only in appearance, but also in its properties and functions.

A group of researchers from the University of Massachusetts studied the contents of cellular vesicles – vesicles that are secreted by the cell. Experiments with fruit flies have shown that motor neurons secrete vesicles containing a high concentration of information RNA (mRNA) of the Arc gene. Both groups found evidence that the "capsid" of the Arc protein contains mRNA and that the "capsids" are separated from neurons as part of vesicles. The more active the neurons, the more such vesicles are released.

Experiments have shown that "capsids" from the Arc protein transmit mRNA to neighboring cells in the same way as viruses do. The researchers cultured neurons of mice without the Arc gene in Petri dishes containing Arc vesicles and Arc "capsids". They found that neurons that previously did not have the Arc gene took mRNA from vesicles and "capsid" and began to synthesize a protein encoded by this gene. With an increase in the electrical activity of neurons, protein production increased and surpassed that of cells originally containing the Arc gene.

It was also found that mRNA moves only in one direction – from motor neurons to muscle cells. The protein encoded by Arc is able to bind only to a certain portion of the mRNA (an untranslated region) that is not used for protein synthesis. Motor neurons of flies that do not have the Arc gene form fewer connections among themselves.

Both groups of researchers plan to determine why cells transmit information in the same way as viruses do, and whether the same pathway is possible for the spread of toxic proteins in the brain in Alzheimer's disease. Research can shed light on the development of neurological diseases and lead to the development of new drugs.

The researchers believe that the Arc "capsid" can be used for genetic engineering and gene therapy, in which viruses are currently actively used to deliver proteins to cells. The immune system often attacks these viruses, which leads to the development of side effects. Since the Arc protein is synthesized in the human body, there will be no immune reaction to it, and it can be used to deliver genes as part of gene therapy.

Article by Elissa D. Pastuzyn et al. The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer and Ashley et al. Retrovirus-like Gag protein Arc1 binds RNA and traffics across synaptic boutons published in the journal Cell.

Arc.jpg
Arc1.jpg
Drawings from articles by Pastuzyn et al. and Ashley et al.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on NINDS: Memory gene goes viral.


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