Original version With this story appeared in Quanta Magazine.
For the RNA molecule, the world is a threatening place. Unlike DNA, which can survive for millions of years in its extremely stable, double-stranded form, RNA is not built to survive – even in the cell that produced it. If it is not securely attached to a larger molecule, the RNA can degrade within minutes or less. And outside the cell? Forget it. Voracious RNA-destroying enzymes are everywhere, secreted by all life forms to defend themselves against viruses that determine their genetic identity in the RNA code.
There is one way that RNA can survive outside the cell unscathed: in a diminutive, protective bubble. For decades, researchers have noticed that cells release cell membrane vesicles, called extracellular vesicles (EVs), filled with degraded RNA, proteins, and other molecules. However, these bags were thought to be little more than garbage bags that removed shredded molecular debris from the cell during routine cleaning.
Then, in the early 21st century, experiments conducted by Hadi Valadimolecular biologist from the University of Gothenburg, revealed that the RNA found in some electric vehicles does not look like garbage. The cocktail of RNA sequences was very different from those found inside the cell, and these sequences were just that intact and functional. When Valadi’s team exposed human cells to EVs derived from mouse cells, they were shocked to observe human cells taking in the RNA messages and “reading” them, creating functional proteins that they otherwise could not make.
Valadi concluded that cells packed RNA strands into vesicles specifically to communicate with each other. “If I was outside and I saw it was raining,” he said, “I could tell you: If you go out, take an umbrella with you.” In a similar way, he suggested, a cell could warn its neighbors about exposure to a pathogen or harmful chemical before they encounter the threat themselves.
Since then, a wealth of evidence has emerged supporting this theory, made possible by improvements in sequencing technology that allow scientists to detect and decode ever smaller segments of RNA. Since Valadi published his experiments, other researchers have also observed EVs loaded with convoluted RNA combinations. These RNA sequences can contain detailed information about the cell that created them and produce specific effects in recipient cells. The findings have led some researchers to suggest that RNA may be a molecular lingua franca that transcends customary taxonomic boundaries and therefore may encode messages that are understandable across the tree of life.
In 2024, recent research revealed additional layers of this story, showing, for example, that along with bacteria and eukaryotic cells archaea also exchange RNA associated with vesicles, confirming that this phenomenon is universal to all three domains of life. Another study expanded our understanding of cellular communication between kingdoms by showing that plants and infecting fungi can do so use packets of havoc-wreaking RNA as a form of co-evolutionary information warfare: the enemy cell reads the RNA and builds self-harming proteins using its own molecular machinery.
“I was impressed by what RNA could do,” he said Amy Buckan RNA biologist at the University of Edinburgh who was not involved in the recent research. According to her, understanding RNA as a means of communication “goes beyond appreciating the sophistication and dynamic nature of RNA in the cell.” Transmitting information outside the cell may be one of its innate roles.
Time sensitive delivery
Microbiologist Zuzanna Erdmann examines viral infections in Haloferax volcanoa single-celled organism that thrives in incredibly salty environments such as the Dead Sea or the Great Salt Lake. Single-cell bacteria are known to list electric vehicles widely, but H. volcanoes is not a bacterium – it is archaica member of the third evolutionary branch of life in which cells are built differently than bacteria or eukaryotes like us.
Because electric vehicles are the same size and density as virus particles, as Erdmann’s team studies at the Max Planck Institute for Marine Microbiology in Germany, “they always show up when you isolate and purify viruses,” she said. Eventually, her group became curious and decided to look inside.