Traditionally, sunburn has been linked to damage caused by UV radiation to DNA. However, recent research from the University of Copenhagen and Nanyang Technological University in Singapore indicates that RNA, another essential cell component, significantly contributes to the immediate reactions seen in sunburn.
We’ve all heard the advice to avoid direct sunlight from noon to 3 p.m., to find shade, and to apply sunscreen and wear hats. Yet, many of us have experienced sunburn at least once, leading to red, irritated skin in need of relief.
While it’s commonly believed that sunburn harms DNA, researchers from a recent study at the University of Copenhagen and NTU Singapore clarify that this view is incomplete.
“Textbooks say that sunburn damages DNA, resulting in cell death and inflammation. However, we were surprised to find that the acute effects of sunburn stem from damage to RNA, not DNA,” explains Assistant Professor Anna Constance Vind from the Department of Cellular and Molecular Medicine and a key contributor to the study.
The research titled ‘The ribotoxic stress response drives acute inflammation, cell death, and epidermal thickening in UV-irradiated skin in vivo’ has been published in Molecular Cell.
RNA shares similarities with DNA, but unlike long-lasting DNA, RNA is more transient. One type of RNA, known as messenger RNA (mRNA), acts as an intermediary that conveys information from DNA to produce proteins, which are the essential components of cells.
“While DNA damage is critical since mutations can be inherited by future cell generations, RNA damage happens frequently and doesn’t result in permanent mutations. Therefore, we previously thought RNA was less important as long as DNA remained intact. In reality, it’s the damage to RNA that initiates the response to UV radiation,” Anna Constance Vind clarifies.
This research was performed on both mice and human skin cells to explore how UV radiation affects the skin and the nature of these damages. The scientists observed similar reactions to UV exposure in both mice and human cells.
An inherent monitoring system for RNA damage
The study shows that damage to mRNA provokes a reaction within ribosomes (the protein complexes that “interpret” the mRNA to create proteins), coordinated by a protein called ZAK-alpha, leading to what is known as the ribotoxic stress response. This can be viewed as a built-in surveillance mechanism in cells that detects RNA damage, initiating inflammatory signals, which in turn attract immune cells, resulting in skin inflammation.
“Our findings indicate that the immediate cellular response after UV exposure is to RNA damage, which triggers both cell death and inflammation. In UV-exposed mice, we observed inflammatory responses and cell death, but when the ZAK gene was removed, these reactions ceased, highlighting ZAK’s crucial role in skin’s response to UV-induced damage,” comments Professor Simon Bekker-Jensen from the Department of Cellular and Molecular Medicine, who is also involved in the study. He adds:
“Essentially, it all hinges on this one response that monitors all protein synthesis occurring within the cells. When RNA is damaged, cells recognize an anomaly, prompting cell death.”
More rapid and efficient responses
The findings of this study reshape our understanding of sunburn and the skin’s defense systems: RNA damage leads to a quicker and more effective response, safeguarding the skin from further harm.
“It’s significant that DNA does not govern the skin’s initial reaction to UV radiation; rather, a different mechanism is at play, operating more swiftly and adeptly. This represents a major shift in perspective,” Anna Constance Vind states.
Understanding how RNA damage functions may ultimately transform our strategies for preventing and treating sunburn.
“Many chronic skin inflammatory conditions can worsen due to sun exposure. Gaining insights into how our skin reacts at a cellular level to UV damage paves the way for innovative treatments for certain enduring skin issues,” notes co-author Dr. Franklin Zhong, an Assistant Professor at NTU’s Lee Kong Chian School of Medicine.
“This new information overturns established views. Most people associate sunburn with DNA damage; it has been accepted knowledge. Now, we need to update our textbooks, which will greatly influence future research on the impact of UV radiation on skin,” concludes Simon Bekker-Jensen.
