Abstract
The exploration of dynamic N6-methyladenosine (m6A) RNA modification in mammalian cells has attracted great interest in recent years. M6A modification plays pivotal roles in multiple biological and pathological processes, including cellular reprogramming, fertility, senescence, and tumorigenesis. In comparison with growing research unraveling the effects of m6A modifications on eukaryotic messenger RNAs, reports of the association between noncoding RNAs and m6A modification are relatively limited. Noncoding RNAs that undergo m6A modification are capable of regulating gene expression and also play an important role in epigenetic regulation. Moreover, the homeostasis of m6A modification can be affected by noncoding RNAs across a broad spectrum of biological activities. Importantly, fine-tuning and interaction between these processes are responsible for cell development, as well as the initiation and progression of the disease. Hence, in this review, we provide an account of recent developments, revealing biological interactions between noncoding RNAs and m6A modification, and discuss the potential clinical applications of interfering with m6A modification.
Highlights
Since the definition of the term “epitranscriptomics”, more than 100 types of RNA modifications have been recognized in living organisms
1.1.1 Writers m6A modification is regulated by a methyltransferase complex, the core subunits of which are composed of Methyltransferase like 3 (METTL3) and Methyltransferase like 14 (METTL14), as well as other auxiliary cofactors, including Wilms tumor 1-associating protein (WTAP), Vir-like m6A methyltransferase associated (VIRMA), RNA binding motif protein 15 (RBM15)/ 15B, Zinc finger CCCH-type containing 13 (ZC3H13), and Also known as CBLL1 (HAKAI)
Similar to mRNAs, long noncoding RNA (lncRNA) are subjected to m6A methylation in various cell lines. m6A residues show a preference for locating in lncRNA transcripts that have been subjected to alternative splicing [19], indicating that m6A deposition may play a potential role in the formation of lncRNA isoforms. m6A methylation sites are welldistributed along transcripts, in comparison to mRNAs modification patterns [27]
Summary
Since the definition of the term “epitranscriptomics”, more than 100 types of RNA modifications have been recognized in living organisms. As an important mechanism of epitranscriptomics, first characterized in the 1970s, N6-methyladenosine (m6A) is the most frequently observed internal chemical modification in eukaryotic mRNA [1,2,3]. Found in the brain, heart, and kidney, and highly conserved between humans and mice, m6A modification mainly lies in the 3’-UTR of mRNAs, near the stop codons and within internal exons [1]. For certain RNA, the accessibility and biological activity of m6A modification very likely influences the outcome of physiological or pathological processes
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