PARP-dependent acetylation of N4-cytidine in RNA appears in UV- damaged chromatin

Abstract

Abstract RNA modifications have been known for many years, but their function has not been fully elucidated yet. For instance, the regulatory role of acetylation on N4-cytidine (ac4C) in RNA should be explored not only from the view of regulation of RNA stability and mRNA translation but also during DNA repair. Here, we observe a pronounced positivity of ac4C RNA at DNA lesions of interphase cells and in irradiated cells in telophase. Ac4C RNA appears in the damaged genome from 2 to 45 minutes after microirradiation. However, RNA cytidine acetyltransferase NAT10 did not accumulate to damaged chromatin. This process was not dependent on the G1, S, and G2 cell cycle phases. Also, we observed that the PARP inhibitor, olaparib, prevents the recruitment of ac4C RNA to DNA lesions. Together, our data imply that acetylation of N4-cytidine in RNA is an important RNA modification that, with a high probability, mediates DNA damage repair. Ac4C RNA likely causes de-condensation of chromatin in the vicinity of DNA lesions accessible for other DNA repair factors playing a role in DNA damage response. Alternatively, RNA modifications, including ac4C, could be markers of damaged RNAs.