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Review
. 2021 Jun 4:9:670711.
doi: 10.3389/fcell.2021.670711. eCollection 2021.

N6-Methyladenosine RNA Modification in Inflammation: Roles, Mechanisms, and Applications

Jiahui Luo  1 , Tao Xu  2 , Kai Sun  3
Affiliations
Review

N6-Methyladenosine RNA Modification in Inflammation: Roles, Mechanisms, and Applications

Jiahui Luo et al. Front Cell Dev Biol. .

Abstract

N6-methyladenosine (m6A) is the most prevalent internal mRNA modification. m6A can be installed by the methyltransferase complex and removed by demethylases, which are involved in regulating post-transcriptional expression of target genes. RNA methylation is linked to various inflammatory states, including autoimmunity, infection, metabolic disease, cancer, neurodegenerative diseases, heart diseases, and bone diseases. However, systematic knowledge of the relationship between m6A modification and inflammation in human diseases remains unclear. In this review, we will discuss the association between m6A modification and inflammatory response in diseases, especially the role, mechanisms, and potential clinical application of m6A as a biomarker and therapeutic target for inflammatory diseases.

Keywords: N6-methyladenosine; RNA modification; epigenetics; inflammation; inflammatory disease.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Dynamic process of RNA N6-methyladenosine methylation. RNA m6A modification is a dynamic and reversible process. m6A can be installed by the methyltransferase complex and removed by demethylases. m6A modifications are enriched in the 3′-untranslated regions (UTRs) near the stop codons of mRNA and within internal long exons, mainly with a consensus sequence of RRACH. m6A participates in almost all processes in mRNA metabolism, including RNA transcription, translation, and degradation.
FIGURE 2
FIGURE 2
Diverse biological consequences of m6A methylation by different m6A “readers.” m6A “readers” can recognize and bind to the m6A modification sites in RNA. They play an important role in different biological functions. The first m6A “readers” identified were YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2, which contain a conserved YTH domain (YT521-B homology). Moreover, three heterogeneous nuclear ribonucleoproteins (hnRNPs) are common “readers,” namely hnRNPC, hnRNPG, and hnRNPA2B1. m6A “readers” are involved in various steps of RNA metabolism, including pre-mRNA splicing, mRNA translation, nuclear export, and mRNA degradation.
FIGURE 3
FIGURE 3
Role of m6A in inflammatory processes of various diseases states. m6A modification affects inflammation by regulating inflammation-related genes. RNA methylation is linked through numerous mechanisms and present in various inflammatory disease states, including autoimmunity, infection, metabolic diseases, and cancer.
FIGURE 4
FIGURE 4
Therapeutic potential based on m6A. The study of epigenetic changes in inflammatory response provides the possibility to develop effective drugs with specific targets based on the m6A regulator.
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