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Review
. 2021 Mar 4;11(9):4549-4566.
doi: 10.7150/thno.54967. eCollection 2021.

The crosstalk between m6A RNA methylation and other epigenetic regulators: a novel perspective in epigenetic remodeling

Yanchun Zhao  1 , Yunhao Chen  2 , Mei Jin  1 , Jin Wang  1
Affiliations
Review

The crosstalk between m6A RNA methylation and other epigenetic regulators: a novel perspective in epigenetic remodeling

Yanchun Zhao et al. Theranostics. .

Abstract

Epigenetic regulation involves a range of sophisticated processes which contribute to heritable alterations in gene expression without altering DNA sequence. Regulatory events predominantly include DNA methylation, chromatin remodeling, histone modifications, non-coding RNAs (ncRNAs), and RNA modification. As the most prevalent RNA modification in eukaryotic cells, N6-methyladenosine (m6A) RNA methylation actively participates in the modulation of RNA metabolism. Notably, accumulating evidence has revealed complicated interrelations occurring between m6A and other well-known epigenetic modifications. Their crosstalk conspicuously triggers epigenetic remodeling, further yielding profound impacts on a variety of physiological and pathological processes, especially tumorigenesis. Herein, we provide an up-to-date review of this emerging hot area of biological research, summarizing the interplay between m6A RNA methylation and other epigenetic regulators, and highlighting their underlying functions in epigenetic reprogramming.

Keywords: DNA methylation; N6-methyladenosine (m6A); RNA modification; chromatin remodeling; histone modification; non-coding RNA (ncRNA).

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
The dynamic and reversible processes of m6A modification. “Writers” deposit m6A methylation on RNAs, while “erasers” remove the m6A marks. Then “readers” are responsible for regulating the fate of targeted RNAs.
Figure 2
Figure 2
The complex interplay between m6A modification and other epigenetic regulators including DNA methylation, chromatin remodeling, histone modification and RNA modification. (A) The regulatory circuit of m6A modification and DNA methylation. (B) The loss of 5mC DNA methylation on METTL3 promotes its expression. (C) m6A methylation affects the chromatin state by regulating the expression of carRNAs. (D) m6A impacts histone modification through modulating the level of histone-associated enzymes. (E) JMJD6 mediates the demethylation of hnRNPA2B1, impelling its translocation to cytoplasm. (F) Histone acetylation facilitates METTL3 expression. (G) m6A methylation and m5C modification cooperatively promote the translation process. (H) Deficiency of m6A methylation leads to the enhanced level of A-to-I editing. (I) m6A methylation regulates the expression of pseudogene and impacts its sponge to miRNA.
Figure 3
Figure 3
The functions and mechanisms of m6A modification on ncRNAs. (A) m6A promotes the maturation of miRNA. (B) m6A modulates lncRNA level. (C) m6A facilitates lncRNA to combine with miRNA. (D) m6A interferes the binding of lncRNA to proteins. (E) m6A mediates the cytoplasmic export of circRNA. (F) m6A regulates circRNA translation. (G) m6A assists the innate immune system to recognize self circRNA.
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