Damaged RNA, not DNA, revealed as main cause of acute sunburn

Sunburn has traditionally been attributed to UV-induced DNA damage, but it turns out that this is not the full truth. That’s according to a study from the University of Copenhagen and Nanyang Technological University, Singapore (NTU Singapore), which has been published in Molecular Cell.

“Sunburn damages the DNA, leading to cell death and inflammation, so the textbooks say,” said Assistant Professor Anna Constance Vind from the University of Copenhagen. “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.”

RNA is similar to DNA, but whereas DNA is long lived, RNA is a more transient molecule. A type of RNA, known as messenger RNA (mRNA), functions as the intermediate ‘messenger’ that carries information from DNA to make proteins — the basic building blocks of cellular components.

“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,” Vind said. “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.”

The new study, which was conducted on mice as well as human skin cells, found that mRNA damage triggers a response in ribosomes (protein complexes that ‘read’ the mRNA to synthesise protein), orchestrated by a protein known as ZAK-alpha — the so-called ribotoxic stress response. The response can be described as a surveillance system within the cells which registers the RNA damage, leading to inflammatory signalling and recruitment of immune cells, which then leads to inflammation of the skin.

“We found that the first thing the cells respond to after being exposed to UV radiation is damage to the RNA, and that this is what triggers cell death and inflammation of the skin,” said Copenhagen’s Professor Simon Bekker-Jensen.

“In mice exposed to UV radiation we found responses such as inflammation and cell death, but when we removed the ZAK gene, these responses disappeared, which means that ZAK plays a key role in the skin’s response to UV-induced damage.

“So you could say that everything depends on this one response, which monitors all protein translations occurring. The cells respond to the RNA damage, realising that something is wrong, and this is what leads to cell death.”

The study thus changes our understanding of sunburn and the skin’s defence mechanisms: that RNA damage triggers a faster and more effective response, protecting the skin from further damage.

“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,” Vind said. This may change our entire approach to the prevention and treatment of sunburn, as well as certain skin conditions that are worsened by sun exposure.

“This new knowledge turns things upside down,” Bekker-Jensen concluded. “I think most people associate sunburn with DNA damage; it is established knowledge. But now we need to rewrite the textbooks, and it will affect future research on the effects of UV radiation on the skin.”

Image credit: iStock.com/Pattarisara Suvichanarakul