RNA traveling from blood to brain

I’m going to try to start blogging regularly about some of the cool papers that I read. Today’s paper is about a newly discovered way that the immune system can affect neurons during inflammation. Immune system cells can send RNA molecules to the brain! It’s not yet clear what impact those RNAs have, but the idea that RNA can travel between cells is still quite new, and I think very exciting.

Stefan Momma’s group wanted to better understand what happens in the brain during inflammation. Others have reported that the immune system can somehow pass on genetic material to neurons, possibly through the cells fusing to each other. Momma’s group wanted to learn more about how the genetic material was transferred. 

Their experimental set-up relies on two clever tricks that biologists use, both of which were stolen from nature (as are the vast majority of biology tricks). One is the bacterial gene LacZ, which when active, turns cells blue. The DNA for this gene was in all cells but kept in an inactive state. To get activated, we need our next biological trick, the Cre gene.

The Cre protein is able to cut DNA at a specific sequence, and in nature it’s found in some viruses. In this experiment, the Cre gene was in all cells, but the protein could only be made in blood cells (but no other cells!). The Cre protein cut away the DNA sequence that inactivated LacZ.

At this point, I assumed the LacZ protein would only be made in blood cells because that’s where the Cre is. And yet! That’s not true. Neurons were also making LacZ, yet there was no sign that the blood cells and neurons were fusing. How was that possible?

As it turns out, there are little balls of fat (vesicles) that travel through the body and can carry cargo with them, like proteins or RNA. These vesicles had no Cre protein in them, but they did have the Cre mRNA in it. Even more interesting, the amount of Cre mRNA increased during inflammation, as did the number of neurons with LacZ.

Since mice don’t generally make Cre, the Cre mRNA is not normally transferred to neurons, yet this study suggests other RNAs could be. No one knows yet what those RNAs are or what they do. Perhaps someday we’ll find out!



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