N6-Adenosine Methylation in RNA and a Reduced m3G/TMG Level in Non-Coding RNAs Appear at Microirradiation-Induced DNA Lesions

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Cells - 9(2020), 2 vom: 04. Feb.

Sprache:

Englisch

Beteiligte Personen:

Svobodová Kovaříková, Alena [VerfasserIn]
Stixová, Lenka [VerfasserIn]
Kovařík, Aleš [VerfasserIn]
Komůrková, Denisa [VerfasserIn]
Legartová, Soňa [VerfasserIn]
Fagherazzi, Paolo [VerfasserIn]
Bártová, Eva [VerfasserIn]

Links:

Volltext

Themen:

12133JR80S
40027-70-1
63231-63-0
Adenosine
CLE6G00625
Chromatin
DNA repair
Epigenetics
Guanosine
Histones
Journal Article
K72T3FS567
METTL-like enzymes
N(2),N(2),7-trimethylguanosine
N-methyladenosine
RNA
RNA, Untranslated
RNA methylation
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 10.02.2021

Date Revised 06.08.2021

published: Electronic

Citation Status MEDLINE

doi:

10.3390/cells9020360

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM306276720