RNA fire alarm

“Inflammation” finds its roots in the Latin verb flammo, “to set on fire,” and it’s an apt descriptor of sunburn. As uncomfortable as it is, sunburn is actually a defense mechanism.  The inflammatory pathway that turns sunburned skin hot and red recruits immune cells to the damaged area.  The thinking goes that immune cells pick off skin cells with DNA damage before anything goes seriously awry (skin cancer).

How do skin cells sound the alarm that they’ve been damaged, as is the case in sunburn?  New research

by Jamie Bernard, a post-doc in Richard Gallo’s lab at University of California, San Diego, and their colleagues shows that damage to small noncoding RNAs can initiate the inflammatory response that’s better known as sunburn.  This is interesting on two fronts: one, we’ve long thought about DNA damage in the context of sunburn, but there’s much less research on UV-induced RNA damage.  Two, it’s another important function now ascribed to non-coding RNAs, once thought of as “junk” since they don’t get translated into proteins.

Bernard and his team found that UVB radiation damaged U1 RNA, a short strand of non-coding RNA in cultured skin cells.  RNA is single-stranded, but U1 RNA has an almost clover-like pattern, with complimentary regions looping around on themselves to create sections of double-stranded RNA.  As it turns out, UVB damage causes duplications of the loops, and these double-stranded fragments activate a protein (TLR3) that turns on inflammatory cytokines IL6 and TNF-alpha.  It also suppresses the immune system, which increases the risk of skin cancer, but can have therapeutic benefits in psoriasis or graft-vs-host transplantation.  In mouse models, the group was able to activate TLR3 simply by injecting UVB-damaged synthetic U1 RNA into the skin.

A few therapeutic treatments could fall out of this research. UVB phototherapy is currently used to treat psoriasis, a disorder in which immune cells stimulate skin cells to proliferate. Phototherapy is effective against psoriasis on several fronts, including toning down immune cell activity.   Maybe we can activate this UV-induced immunosuppression without the UV-aspect. This would reduce risk of skin cancer and eye damage.  Or, as the authors point out, by blocking the body’s ability to recognize bits of damaged RNA, these findings may help people that are especially sensitive to light, such as those with lupus.

In these sunny summer months, I find it a good reminder to use my sunscreen.

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