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Sunburn Results from Damaged Noncoding RNA

07/13/2012
Andrew S. Wiecek

Using RNA-seq to identify structural changes to the transcriptome, researchers have discovered how UV light triggers the immune reaction known as a sunburn.


If you happen to find time this summer to escape from the fluorescent lights of the lab for some fun in the sun, don’t forget to apply sunscreen. According to a new study from the University of California, San Diego (UCSD), your noncoding RNA is at stake.

Using RNA-seq to identify structural changes to the transcriptome, researchers have discovered how UV light triggers the immune reaction known as a sunburn. Source: Thomas Deerinck, National Center for Microscopy and Imaging Research, UCSD.





In a study published online at Nature Medicine last week (1), a team led by UCSD dermatologist Richard Gallo described molecular mechanisms behind the inflammatory response known as sunburn. As it turns out, UV light damages noncoding RNA in skin cells, which then trigger an immune response from the surrounding cells.

“We were quite surprised and excited to learn that the one particularly abundant noncoding RNA, whose function is not particularly well understood, could be involved in the biological process of the sunburn reaction,” said Gallo.

To identify the specific noncoding RNAs that were affected by exposure to UV radiation, the scientists turned to next-generation whole-transcriptome shotgun sequencing, commonly referred to as RNA-seq. By sequencing the transcriptome of skin cells before and after UV exposure, Gallo’s team found that the sequence frequency of one particular noncoding RNA, called U1 RNA, increased by almost 20%.

“It was really a concept that we and our collaborators came up with on our own. RNA-seq relies on primer hybridizations that depend on structure. So, if the structure is altered, we would be able to see that in the change in the the frequency of the reads. And that’s when it came up with that these noncoding RNAs that were changed by UV light,” said Gallo.

Upon further investigation, the researchers found that UV exposure actually affected the sequence, and therefore structure, of the the U1 loop domains of these RNAs. Previous research had suggested that the U1 RNA could be involved in some way with autoimmune responses.

In addition, the researchers tested their hypothesis in both human cells and mouse models to confirm their findings. In one experiment with cultured human skin cells, Gallo and colleagues found that synthetic U1 RNA that had been exposed to UV radiation triggered an immune response in cultured human skin cells, but non-irradiated synthetic U1 RNA did not. Likewise, the UV-irradiation RNA produced an inflammatory response on the skin of mouse models, while the non-irradiated synthetic RNA did not.

“We switched between the mouse models and the human models because mice are not always perfect models. But with RNA silencing techniques, we were able to validate much of the research in the mouse model. It’s always reassuring to validate findings in humans cells,” said Gallo.

In the end, the researchers are now following up on several translational avenues of investigation stemming from this study. For one, Gallo’s team is looking at how this inflammatory reaction relates to the cancerous effects of sun exposure. Also, because UV radiation is used as a treatment for various dermatological diseases, this research could help researchers understand how those treatments work and possibly bypass the radiation part to avoid the dangerous side-effects.

References

1. Bernard, J. J., C. Cowing-Zitron, T. Nakatsuji, B. Muehleisen, J. Muto, A. W. Borkowski, L. Martinez, E. L. Greidinger, B. D. Yu, and R. L. Gallo. 2012. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat Med advance online publication(July).

08/03/2012, Correction: A previous version of this article identified U1 as a microRNA when, in fact, it is a small nuclear noncoding RNA.

Keywords:  microRNA noncoding RNA