A NEWLY published study has identified a previously underappreciated RNA-based mechanism that protects skin from photoageing, offering fresh insight into how chronic ultraviolet (UV) exposure accelerates skin ageing and collagen loss.
RNA Stability Emerges as a New Target in Skin Ageing
Photoageing, a major form of extrinsic skin ageing, is driven primarily by long-term UV irradiation and is characterised by wrinkles, reduced collagen, and cellular senescence. While transfer RNA-derived small RNAs (tsRNAs) have been linked to ageing, inflammation, and oxidative stress, their specific role in photoageing has remained unclear. In this study, researchers investigated the function of a specific tRNA-derived fragment, tRF-34, and its underlying molecular mechanisms.
Using primary human dermal fibroblasts (HDFs), murine skin models, and sun-exposed human skin samples, the researchers demonstrated that tRF-34 expression was significantly reduced following chronic UVA1 exposure. This downregulation was confirmed using RT-qPCR and fluorescence in situ hybridisation. Functionally, restoring tRF-34 levels in UVA1-irradiated fibroblasts reduced hallmark features of photoageing, including cellular senescence, while inhibition of tRF-34 worsened these ageing-related changes.
Mechanistic analyses revealed that tRF-34 binds directly to the RNA-binding protein YTHDF2, a known mediator of N6-methyladenosine (m⁶A)-dependent mRNA degradation. By interacting with YTHDF2, tRF-34 inhibited the degradation of natriuretic peptide receptor C (NPRC) mRNA, thereby stabilising its expression. Notably, NPRC levels were also found to be diminished in photoaged skin.
Could RNA Therapeutics Transform Photoageing Treatment?
Further investigation showed that NPRC exerted protective effects against photoageing by activating the TGF-β1/Smad signalling pathway, a key regulator of collagen synthesis and skin homeostasis. This signalling cascade is known to decline with UV-induced ageing, linking the tRF-34 pathway directly to collagen preservation.
In vivo experiments reinforced these findings. Overexpression of tRF-34 in a mouse model exposed to chronic UVA1 irradiation significantly reduced wrinkle formation and improved dermal collagen content compared with controls.
The authors conclude that the newly identified tRF-34/YTHDF2/NPRC regulatory axis plays a critical role in maintaining skin integrity under chronic UV stress. These findings not only expand current understanding of tsRNA biology in skin ageing but also highlight tRF-34 as a potential therapeutic target for preventing or treating photoageing.
Reference
Dai X et al. A tRNA-derived RNA fragment protects skin from photoaging by preserving collagen and mRNA stability. Br J Dermatol. 2026;doi: 10.1093/bjd/ljag046.
