Emerging roles of RNA as a driver of UV-induced skin inflammation and inflammatory skin disease

Ultraviolet (UV) radiation is a major environmental trigger of cutaneous inflammation. While DNA damage has long been considered the main mediator of UV pathology, a growing body of evidence indicates that RNA is a primary driver of UV-induced inflammation. UV exposure induces RNA damage and dysregulates RNA metabolism, activating the ribotoxic stress response and promoting the generation and accumulation of immunostimulatory self-RNAs. RNA metabolism also plays a role in UV-related dermatologic pathologies, including photosensitive inflammatory skin disorders and skin carcinogenesis. In this review, we summarize current knowledge and new advances on the role of RNA in UV-induced inflammation, with an emphasis on both mechanisms and translational implications. Together, these insights suggest that targeting RNA pathways may represent a new approach for treating or preventing UV-induced skin inflammation and inflammatory skin disease.