For decades, we’ve believed the bright redness of sunburn — along with its irritating sting and peeling skin — was the result of ultraviolet (UV) radiation wreaking havoc on DNA. But now, a new study from researchers at the University of Copenhagen and Nanyang Technological University in Singapore suggests otherwise. The redness, inflammation, and pain of sunburn may stem from damage to RNA, not DNA.
“Sunburn damages the DNA, leading to cell death and inflammation. So the textbooks say,” said Assistant Professor Anna Constance Vind, one of the study’s lead researchers. “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.”
This discovery rewrites the rules of how our skin reacts to UV exposure. And it points to a sophisticated cellular defense mechanism hidden in plain sight.
RNA’s Day in the Sun
The RNA molecule is often overshadowed by its more famous counterpart DNA, but despite its more intermediary role, it’s no less important. RNA translates DNA’s genetic instructions into proteins — the building blocks of life. Unlike DNA, which is permanent and prone to dangerous mutations, RNA is disposable and replaced frequently. For this reason, RNA damage has always taken a backseat regarding cellular stress responses.
But Vind and her colleagues uncovered a different story. They found that RNA damage triggers a swift cellular response through a protein called ZAK-alpha, which acts as a molecular watchdog. When RNA is damaged by UV rays, ZAK-alpha initiates a chain reaction known as the ribotoxic stress response (RSR). Unlike the well-known DNA damage response, RSR is triggered when ribosomes encounter damaged RNA. This leads to inflammation, cell death, and recruitment of immune cells to the site of the 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.
What exactly happens? RNA Damage as a First Responder
To uncover this story, the researchers used genetically modified mice and human skin cells. In normal mice, UVB exposure activated the ZAK-alpha protein, which senses ribosomal distress. This set off a cascade of inflammatory signals, recruiting immune cells to the skin and driving programmed cell death. But in mice lacking the ZAK gene, these responses were muted and there were no sunburn-like effects. This suggests that the ribotoxic stress response plays a pivotal role in sunburn reactions.
Human keratinocytes, the cells forming the skin’s outermost layer, showed a similar reliance on ZAK-alpha. The study revealed that two distinct processes unfolded: pyroptosis, a fiery and inflammatory form of cell death, and apoptosis, a quieter, programmed cell death. In both cases, ZAK-alpha was at the helm.
“So you could say that everything depends on this one response, which monitors all protein translations occurring,” said Professor Simon Bekker-Jensen, another key researcher on the study. “The cells respond to the RNA damage, realizing that something is wrong, and this is what leads to cell death.”
Why It Matters
This discovery shifts the paradigm of how we understand UV damage. It explains why inflammation happens so quickly after sun exposure — ribosomes can react to RNA stress within hours, while DNA repair pathways may take longer. This naturally opens new avenues for skincare and sun protection. Suppose scientists can target the ribotoxic stress response. In that case, they may be able to develop treatments that reduce the painful inflammation of sunburn or even prevent the thickening of the skin that occurs with chronic UV exposure.
Moreover, the study raises intriguing questions about the broader role of ZAKα and the RSR. Could they be implicated in other conditions, such as inflammatory skin diseases like psoriasis? Early experiments suggest that the ribotoxic stress response might explain some symptoms of such disorders, though more research is needed.
“Many inflammatory skin diseases are worsened by sun exposure. Thus, understanding how our skin responds at the cellular level to UV damage opens the door to innovative treatments for certain chronic skin conditions,” said Dr. Franklin Zhong, a co-author of the study.
However, the role of DNA damage in skin health should not be discounted.
DNA still damage still happens
UV-induced DNA damage remains a well-established pathway leading to long-term consequences, including premature aging and skin cancer. The formation of DNA photoproducts, such as thymine dimers, can disrupt the genetic code, triggering mutations that accumulate over time.
These mutations can impair cellular function and, in some cases, drive the development of malignancies. RNA is involved in immediate, short-term damage to the skin, while DNA damage is related to chronic UV-related skin conditions in the long term.
Even as scientists work toward innovative treatments, the basics remain the same: sunscreen, shade, and protective clothing are still the best ways to protect yourself from UV rays.
The findings appeared in the journal Molecular Cell.
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