Study suggests RNA, not DNA, triggers the first moments of sunburn

Spending too long in the sunshine without proper protection can leave us looking - and likely feeling - like a lobster ready to be served.

For years, the standard account of why sunburn hurts has focused on a chain reaction that begins when UV exposure breaks the skin’s DNA, setting off inflammation.

A new study using mice and human skin cells suggests that crucial detail may have been wrong. The research indicates that the very first steps of sunburn unfold differently than most people - and many textbooks - have assumed.

"Sunburn damages the DNA, leading to cell death and inflammation. So the textbooks say," says Anna Constance Vind, a molecular biologist at the University of Copenhagen who led work challenging that long-held view.

"But in this study we were surprised to learn that this is a result of damage to the RNA, not the DNA that causes the acute effects of sunburn."

Sunburn and ultraviolet B radiation

Despite the name, sunburn is not quite the same as a mild thermal burn. Heat damage primarily involves proteins being disrupted by high temperatures, whereas sunburn is driven by extended exposure to shorter-wavelength ultraviolet B (UVB) radiation.

Whatever the source of injury, the outcome is familiar: multiple forms of cellular stress signal danger to the immune system. That warning sets off a cascading series of chemical alarms that dilate some blood vessels, constrict others, and heighten sensitivity to pain.

Working out exactly what flips the switch is complicated. Heat itself can provoke stress responses. Abrupt shifts in cellular water balance, reactive oxygen species released by damaged compounds, and even straightforward physical disruption of cells can all prompt the immune system to respond urgently.

Why RNA damage may trigger the initial sunburn response

Because ultraviolet B photons can be absorbed by bonds between nucleic bases - to the point that those bonds break and re-form - researchers have long assumed that DNA damage, alongside other kinds of cellular injury, is essential in kick-starting early signalling.

"DNA damage is serious as the mutations will get passed down to progenies of the cells, RNA damage happens all the time and does not cause permanent mutations," says Vind.

"Therefore, we used to believe that the RNA is less important, as long as the DNA is intact. But in fact, damages to the RNA are the first to trigger a response to UV radiation."

ZAK-alpha, mice, and the RNA stress response

To test this, Vind and colleagues used mice genetically engineered to lack a stress-response protein known as ZAK-alpha. This protein interacts with the cellular machinery that translates messenger RNA into proteins, effectively raising the alarm when translation is disrupted.

When the team exposed mice with and without ZAK-alpha to ultraviolet B - or gave them an antibiotic that also activates this protein’s response - the results pointed to an RNA-mediated stress response as a key driver of the symptoms we associate with sunburn.

Alongside this, a set of laboratory experiments in human skin cells examined what happens when UV exposure induces DNA damage. Across these tests, the researchers found that major changes to a cell’s messenger RNA were linked to the cell shutting down and to an immune response being initiated.

Notably, mice exposed to ultraviolet B without ZAK-alpha did not burn in the usual way. That finding implies RNA damage may be central not only to the inflammatory response itself, but also to how sensitive bodies are to sunlight.

What a shift from DNA to RNA could mean

Although harm to the body’s core DNA “library” is understandably the more worrying prospect, keeping tabs on the messenger system may allow cells to react faster when radiation threatens.

"The fact that the DNA does not control the skin's initial response to UV radiation, but that something else does and that it does so more effectively and more quickly, is quite the paradigm shift," says Vind.

By continuing to investigate the effects of RNA damage and how it contributes to stress responses, researchers may uncover improved ways to treat sunburn and other conditions made worse by sunlight.

This research was published in Molecular Cell.