Abstract
The DNA damage response is mediated by both DNA repair proteins and epigenetic markers. Here, we observe that N6-methyladenosine (m6A), a mark of the epitranscriptome, was common in RNAs accumulated at UV-damaged chromatin; however, inhibitors of RNA polymerases I and II did not affect the m6A RNA level at the irradiated genomic regions. After genome injury, m6A RNAs either diffused to the damaged chromatin or appeared at the lesions enzymatically. DNA damage did not change the levels of METTL3 and METTL14 methyltransferases. In a subset of irradiated cells, only the METTL16 enzyme, responsible for m6A in non-coding RNAs as well as for splicing regulation, was recruited to microirradiated sites. Importantly, the levels of the studied splicing factors were not changed by UVA light. Overall, if the appearance of m6A RNAs at DNA lesions is regulated enzymatically, this process must be mediated via the coregulatory function of METTL-like enzymes. This event is additionally accompanied by radiation-induced depletion of 2,2,7-methylguanosine (m3G/TMG) in RNA. Moreover, UV-irradiation also decreases the global cellular level of N1-methyladenosine (m1A) in RNAs. Based on these results, we prefer a model in which m6A RNAs rapidly respond to radiation-induced stress and diffuse to the damaged sites. The level of both (m1A) RNAs and m3G/TMG in RNAs is reduced as a consequence of DNA damage, recognized by the nucleotide excision repair mechanism.
Highlights
Focusing on epigenetic features, it has been established that DNA methylation, posttranscriptional modifications of RNAs, and posttranslational modifications (PTMs) of histones are essential for genome functions
In the locally microirradiated region of interest (ROI), we studied the level of the following epigenetic markers as well as markers of DNA damage: m6 A RNAs, METTL3, METTL14, methyltransferase-like 16 (METTL16), FTO, γH2AX, UBF1/2, fibrillarin, cyclobutane pyrimidine dimers (CPDs), m3 G/TMG RNAs, and m1 A RNA
Such methylated RNAs diffuse to CPD sites, characterized by a high level of repair factors, including DNA methyltransferase 1 (DNMT1) [61], and HP1β that binds to H3K9me3 as well as playing a role in nucleotide excision repair (NER) [54,62]
Summary
It has been established that DNA methylation, posttranscriptional modifications of RNAs, and posttranslational modifications (PTMs) of histones are essential for genome functions. It has been found that m6 A RNA occupies the 30 -untranslated regions (30 -UTRs) and is located near the stop codon of the mRNA [9,10,11]. To some extent, this posttranscriptional modification affects pre-mRNA splicing, RNA degradation, and specific protein–RNA interactions [5,12,13,14]. M6 A can appear in transfer RNA (tRNA), Cells 2020, 9, 360; doi:10.3390/cells9020360 www.mdpi.com/journal/cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
