Abstract

Epigenetic modifications on individual bases in DNA and RNA can encode inheritable genetic information beyond the canonical bases. Among the nucleic acid modifications, DNA N6-methadenine (6mA) and RNA N6-methyladenosine (m6A) have recently been well-studied due to the technological development of detection strategies and the functional identification of modification enzymes. The current findings demonstrate a wide spectrum of 6mA and m6A distributions from prokaryotes to eukaryotes and critical roles in multiple cellular processes. It is interesting that the processes of modification in which the methyl group is added to adenine and adenosine are the same, but the outcomes of these modifications in terms of their physiological impacts in organisms are quite different. In this review, we summarize the latest progress in the study of enzymes involved in the 6mA and m6A methylation machinery, including methyltransferases and demethylases, and their functions in various biological pathways. In particular, we focus on the mechanisms by which 6mA and m6A regulate the expression of target genes, and we highlight the future challenges in epigenetic regulation.

Highlights

  • Covalent modifications on nucleotides, including DNA and RNA, have expanded the genetic codes beyond their canonical bases to accomplish biological functions in multiple cellular processes in organisms [1].At the DNA level, 5-methylcytosine (5mC) in CpG dinucleotides, the most abundantly modified DNA base, has been widely studied in eukaryotes and can regulate the expression of numerous genes by functioning as an epigenetic regulator [2,3,4,5]

  • We identified the homologous proteins of DNA N6 adenine methyltransferase 1 (DAMT-1) and methyltransferase-like 4 (METTL4) in insects and the phylogeny analysis showed a high similarity of METTL4 among eukaryotic species [14]

  • Genome-wide mapping of DNA 6mA methylation and transcriptome-wide analysis of RNA m6A methylation have advanced our understanding of the roles of these two kinds of modifications in multiple biological processes in prokaryotes and eukaryotes

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Summary

Introduction

Covalent modifications on nucleotides, including DNA and RNA, have expanded the genetic codes beyond their canonical bases to accomplish biological functions in multiple cellular processes in organisms [1]. N6-methyladenosine (m6A) is the most prevalent modification on RNA molecules It was first discovered in 1974 in mRNA from cancer cells [25] and was subsequently identified in various species, such as viruses [26,27], bacteria [28], Streptococcus pneumoniae [28], Saccharomyces cerevisiae [29], Thermus thermophiles, D. melanogaster [30,31,32], B. mori [33], Triticum aestivum [34], Zea mays [35], Avena sativa [36], A. thaliana [37,38], S. scrofa [39], M. musculus [40,41], and H. sapiens [40,42]. We will focus on the current progress in research on these two kinds of methylation, with particular attention to the mechanisms by which DNA 6mA and RNA m6A regulate the expression of target genes

Enzymes for DNA 6mA Methylation
Functions of DNA 6mA Methylation
Functions of RNA m6A Methylation
Findings
Conclusions and Perspectives

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