The Crucial Role of RNA Damage in Unraveling Sunburn Reactions

Historically, sunburn has been linked to DNA damage induced by UV light. However, a recent investigation by the University of Copenhagen and Nanyang Technological University, Singapore, uncovers that RNA, a crucial cellular element, significantly contributes to initiating acute sunburn responses.

We have all received advice to steer clear of direct sunlight between 12 noon and 3 p.m., seek shade, and apply sunscreen and a hat. Yet, a vast majority of us have experienced sunburn at least once, resulting in skin that turns vivid red, feels sore, and requires cooling.

You may have also been informed that sunburn inflicts damage on DNA. However, this does not tell the whole story, according to the researchers behind this new study conducted at the University of Copenhagen and Nanyang Technological University, Singapore (NTU Singapore).

“Sunburn injures the DNA, resulting in cellular death and inflammation. At least, that is what textbooks assert. However, in this investigation, we were astonished to discover that it is the harm to RNA, not DNA, that instigates the acute consequences of sunburn,” states Assistant Professor Anna Constance Vind from the Department of Cellular and Molecular Medicine, who is one of the researchers behind the new 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.

While RNA is akin to DNA, DNA is long-lasting, whereas RNA is a more fleeting molecule. A form of RNA, known as messenger RNA (mRNA), acts as the intermediary ‘messenger’ that conveys information from DNA to synthesize proteins – essential building blocks of cellular components.

“DNA damage is grave since the mutations can be inherited by the cellular progeny, while RNA damage is a frequent occurrence and does not lead to permanent mutations. Thus, we used to consider RNA less critical, as long as DNA remains unscathed. Yet, in reality, it is the damage to RNA that first triggers a response to UV radiation.”

Anna Constance Vind, Assistant Professor, Department of Cellular and Molecular Medicine

This new investigation was performed using both mice and human skin cells, aiming to elucidate the effect of UV radiation on the skin and the underlying causes of these injuries. The research team observed that the skin’s reaction to UV exposure is consistent in both mice and human cells.

An intrinsic surveillance mechanism for RNA damage

Damage to mRNA activates a reaction in ribosomes (protein complexes that “interpret” the mRNA to produce proteins), coordinated by a protein called ZAK-alpha – referred to as the ribotoxic stress response – as indicated by the new study. This response can be characterized as a surveillance mechanism within the cells, which acknowledges the RNA damage, leading to inflammatory signals and the enlistment of immune cells, consequently triggering skin inflammation.

“We discovered that the initial reaction of the cells after exposure to UV radiation is the injury to RNA, and this is what instigates cell death and inflammation of the skin. In mice subjected to UV radiation, we observed responses like inflammation and cell death, but when we eliminated the ZAK gene, these responses vanished, indicating that ZAK plays a vital role in the skin’s reaction to UV-induced harm,” explains Professor Simon Bekker-Jensen from the Department of Cellular and Molecular Medicine, another researcher involved in the study. He adds:

“Thus, you could assert that everything hinges on this one response, which oversees all protein translations occurring. The cells recognize the RNA damage, understanding that something is amiss, and this ultimately leads to cell death.”

Quicker and more effective response

The findings of the study alter our comprehension of sunburn and the skin’s protective mechanisms: RNA damage initiates a quicker and more effective response, shielding the skin from additional harm.

“The revelation that DNA does not govern the skin’s initial reaction to UV radiation, but that another factor does so in a more effective and prompt manner, represents a significant shift in understanding,” states Anna Constance Vind.

Understanding the role of RNA damage is crucial, as it may fundamentally change our future strategies for the prevention and treatment of sunburn.

“Numerous inflammatory skin ailments are exacerbated by sun exposure. Therefore, comprehending how our skin reacts at the cellular level to UV damage opens the door for innovative treatments for certain chronic skin disorders,” remarks co-author Dr. Franklin Zhong, Nanyang Assistant Professor at NTU’s Lee Kong Chian School of Medicine.

“This newfound understanding flips conventional views. I believe most people equate sunburn with DNA damage; it is widely accepted knowledge. However, we will need to revise the textbooks, which will influence forthcoming research on the impact of UV radiation on the skin,” concludes Simon Bekker-Jensen.