The significance of N6-methyladenosine-modified non-coding RNAs in different disorders

N6-methyladenosine (m6A) is a methylation mark that occurs in the N6-position of adenosine. As the most widespread internal modification of eukaryotic mRNA, m6A can affect gene expression, thereby contributing to the regulation of diverse cellular processes. This methylation mark is installed by m6A methyltransferase and eliminated by m6A demethylase (He et al., 2019). m6A is mostly detected adjacent to the stop codon, 3′-untranslated regions, and long internal exons (Dominissini et al., 2012). The presence of this methylation mark can affect the expression of target genes, therefore altering their physiological functions. Mechanistically, m6A contributes to nearly all phases of RNA metabolism, such as mRNA translation, degradation, splicing, export, and folding (Fig. 1) (Liu and Gregory, 2019). Therefore, it is not surprising that m6A participates in the pathology of various cancers (He et al., 2019).

Recent studies have shown that m6A marks within non-coding RNAs can affect their functions and expression in a way similar to mRNA-coding genes. Since non-coding RNAs are involved in the pathophysiology of several disorders, identifying the role of m6A marks in the regulation of non-coding RNA expression can usher in a new era for recognizing underlying mechanisms of several disorders and designing novel therapeutic modalities for a variety of disorders, particularly cancers. Meanwhile, the presence of m6A marks can be influenced by several non-coding RNAs.

In the current review, we highlight the effects of m6A marks on the expression of non-coding RNAs and the importance of these transcripts in the regulation of m6A marks in the context of different disorders, including bone, gastrointestinal, neurologic, renal, pulmonary, hepatic and other disorders.

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