N6-Methyladenosine, DNA Repair, and Genome Stability.

Fei Qu,Pawlos S Tsegay,Yuan Liu

doi:10.3389/fmolb.2021.645823

Fei Qu, Pawlos S Tsegay + Show 1 more

Open Access

https://doi.org/10.3389/fmolb.2021.645823

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Abstract

N6-methyladenosine (m6A) modification in mRNAs and non-coding RNAs is a newly identified epitranscriptomic mark. It provides a fine-tuning of gene expression to serve as a cellular response to endogenous and exogenous stimuli. m6A is involved in regulating genes in multiple cellular pathways and functions, including circadian rhythm, cell renewal, differentiation, neurogenesis, immunity, among others. Disruption of m6A regulation is associated with cancer, obesity, and immune diseases. Recent studies have shown that m6A can be induced by oxidative stress and DNA damage to regulate DNA repair. Also, deficiency of the m6A eraser, fat mass obesity-associated protein (FTO) can increase cellular sensitivity to genotoxicants. These findings shed light on the novel roles of m6A in modulating DNA repair and genome integrity and stability through responding to DNA damage. In this mini-review, we discuss recent progress in the understanding of a unique role of m6As in mRNAs, lncRNAs, and microRNAs in DNA damage response and regulation of DNA repair and genome integrity and instability.

Highlights

N6-methyladenosine (m6A) is one of the most abundant epitranscriptomic marks in mRNA of eukaryotic cells that occurs at the consensus motif, RRACH (R is G or A or U, and H is U, A, or C) (Dominissini et al, 2012; Meyer et al, 2012; Zhao et al, 2017)
It is regulated by its writer, adenosine methyltransferase, METTL3/ METTL14 and erasers, RNA demethylases, fat mass obesity-associated protein (FTO), and Alk B homolog 5 (ALKBH5). m6A is usually present at the 5′- and 3′-untranslated regions (5′- and 3′-UTRs) and proteinencoding sequences of mRNAs (Svobodova Kovarikova et al, 2020; Wang et al, 2020)
Its cellular functions have not been extensively explored until 2012, when the methylated RNA immunoprecipitation-sequencing (MeRIP-seq) became available for its genome mapping, and its writers, erasers, and readers were discovered (Meyer and Jaffrey, 2017). In this mini-review, we focus on recent progress in understanding the function of m6A in mRNA, long-noncoding RNAs (lncRNAs), and microRNAs and its unique role in regulating DNA repair and genome stability

Summary

Introduction

N6-methyladenosine (m6A) is one of the most abundant epitranscriptomic marks in mRNA of eukaryotic cells that occurs at the consensus motif, RRACH (R is G or A or U, and H is U, A, or C) (Dominissini et al, 2012; Meyer et al, 2012; Zhao et al, 2017). In this mini-review, we focus on recent progress in understanding the function of m6A in mRNA, lncRNAs, and microRNAs and its unique role in regulating DNA repair and genome stability. The results suggest that m6A plays a distinct role in regulating the formation of R-loops, DNA damage, and genome stability in different types of cells.

Results

Conclusion