Now that has spring has sprung, many of us are quickly remembering not only how much we missed the sunshine, but also that we forgot to stock up on aloe vera to soothe that fresh sunburn. Attesting to the utility of a good spot treatment, the lab of Yang Shi at Harvard Medical School reveals that after exposure to ultraviolet (UV) rays, our cells selectively apply a DNA polymerase to repair damage with a little help from some rapid RNA methylation.
The N6-methyladenosine (m6A) modification regulates not only the fate and function of RNA, but also cellular processes like heat shock. Here’s what the talented team found by using immunofluorescence microscopy to visualize the results of UV laser micro-irradiation of U2OS cells:
- After UV radiation, m6A rapidly accumulates on RNA with poly(A) tails at DNA damage sites, which are represented by the γH2A.X histone modification.
- m6A accumulation peaks at 2 minutes and diminishes after just 8 minutes.
- The m6A methyltransferase METTL3 localizes to sites of DNA damage in just 2 minutes, and a knockout (KO) of the catalytic site demonstrates that the accumulation of m6A at DNA damage is dependent on it.
- The m6A demethylase FTO also localizes to sites of DNA damage and a KO results in an increased m6A levels that also last longer after UV irradiation.
- Since the METLL3 KO cells show delayed repair of DNA damage (cyclobutane pyrimidine dimers), the team examined the enzyme that repairs them – DNA polymerase κ (Pol κ) – and discovered that its localization to DNA damage depends on the catalytic activity of METTL3.
- Attesting to the function, overexpression of Pol κ attenuated the altered DNA damage repair in METTL3 KO cells.
Overall, it seems that m6a modification of RNA rapidly accumulates at sites of DNA damage caused by UV and functions as a “beacon” for Pol κ to soothe the burn by repairing damage and thus keep the cell alive. So, the next time you’re peeling away all the apoptosis caused by a bad sunburn, thank m6A that it isn’t worse.
Go learn how m6A can soothe your molecular sunburns over at Nature, March 2017