the original version of this story appeared in Quanta Magazine.
For an RNA molecule, the world is a dangerous place. Unlike DNA, which can persist for millions of years in its remarkably stable double-stranded form, RNA is not designed to last, even within the cell that produced it. Unless protectively attached to a larger molecule, RNA can degrade within minutes or less. And outside a cell? Forget it. There are voracious RNA-destroying enzymes everywhere, secreted by all life forms as a defense against viruses that explain their genetic identity in the RNA code.
There is one way RNA can survive unscathed outside a cell: in a small protective bubble. For decades, researchers have watched cells release these cell membrane bubbles, called extracellular vesicles (EVs), filled with degraded RNA, proteins, and other molecules. But these sacks were considered little more than garbage bags that carried broken down molecular garbage out of a cell during routine cleaning.
Then, in the early 2000s, experiments led by Hadi ValadiMolecular biologist at the University of Gothenburg, revealed that the RNA inside some EVs did not look like garbage. The cocktail of RNA sequences was considerably different from those found inside the cell, and these sequences were intact and functional. When Valadi’s team exposed human cells to EVs from mouse cells, they were surprised to see that the human cells picked up the RNA messages and “read” them to create functional proteins that they otherwise would not have been able to produce.
Valadi concluded that cells packaged RNA strands into vesicles specifically to communicate with each other. “If I’ve been outside and I see that it’s raining,” he said, “I can tell you: If you go out, take an umbrella with you.” Similarly, he suggested, a cell could warn its neighbors about exposure to a pathogen or harmful chemical before they themselves encountered danger.
A wealth of evidence has since emerged supporting this theory, thanks to improvements in sequencing technology that allow scientists to detect and decode smaller and smaller segments of RNA. Since Valadi published his experiments, other researchers have also seen EVs filled with complex combinations of RNA. These RNA sequences can contain detailed information about the cell that created them and trigger specific effects in recipient cells. The findings have led some researchers to suggest that RNA may be a molecular lingua franca that transcends traditional taxonomic boundaries and can therefore encode messages that remain intelligible across the tree of life.
In 2024, new studies have exposed additional layers of this story, showing, for example, that along with bacteria and eukaryotic cells, archaea also exchange RNA bound to vesicles, confirming that the phenomenon is universal in all three domains of life. Another study has expanded our understanding of cellular communication between kingdoms by showing that infecting plants and fungi can use RNA packets that wreak havoc as a form of coevolutionary information warfare: an enemy cell reads the RNA and builds self-destructive proteins with its own molecular machinery.
“I’ve been amazed at what RNA can do,” he said. Amy Buckan RNA biologist at the University of Edinburgh who was not involved in the new research. For her, understanding RNA as a means of communication “goes beyond appreciating the sophistication and dynamic nature of RNA within the cell.” Transmitting information beyond the cell may be one of its innate functions.
Express delivery
the microbiologist Susanne Erdmann studies viral infections in Haloferax volcaniia single-celled organism that thrives in incredibly salty environments like the Dead Sea or the Great Salt Lake. Single-celled bacteria are known to exchange EVs extensively, but H. volcanii It’s not a bacteria, it’s a archaica member of the third evolutionary branch of life, featuring cells built differently than bacteria or eukaryotes like us.
Because EVs have the same size and density as the virus particles that Erdmann’s team studies at the Max Planck Institute for Marine Microbiology in Germany, “they always appear when viruses are isolated and purified,” he said. Finally, his group became curious and decided to take a look at what was inside.
