Abstract
Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved RNA modification. It functions in various aspects of developmental and disease states, by controlling RNA metabolism, such as stability and translation. Similar to other epigenetic processes, m6A modification is regulated by specific enzymes, including writers (methyltransferases), erasers (demethylases), and readers (m6A-binding proteins). As this is a reversible enzymatic process, metabolites can directly influence the flux of this reaction by serving as substrates and/or allosteric regulators. In this review, we will discuss recent understanding of the regulation of m6A RNA modification by metabolites, nutrients, and cellular metabolic pathways.
Highlights
RNA plays an essential role in gene expression control
Synthesis is promoted by growth factor and nutrient-activated signaling pathways [54,55,56], increased it is possible that in growth-promoting conditions, increased substrate and methyl donor (SAM) levels cooperate for maximal ribosomal RNA (rRNA) methylation
Derivatives (NAD+, NADH, nicotinamide adenine dinucleotide phosphate (NADP)+ and NADPH) are structurally similar, NADPH was the strongest binding partner and activator of Fat mass and obesity-associated protein (FTO), followed by NADH. This indicates that the reducing potential of NADPH and NADH may be used for demethylation reactions
Summary
RNA plays an essential role in gene expression control. In addition to transferring genetic information from DNA to protein, RNA controls protein expression by providing messenger RNA (mRNA) for translation. mRNA is generated by the processing of nascent. A variety of m6 A binding proteins (readers) are recruited (Figure 1A) These include YT521-B homology domain family proteins (YTHDF and YTHDC) [44], heterogeneous nuclear ribonucleoproteins (HNRNP) [45], and insulin-like growth factor 2 mRNA-binding protein (IGF2BP) families [20]. These proteins control the fate of target RNAs, such as folding into secondary structures [45], splicing [18], nuclear export [22], liquid–liquid phase separation [46], stability [20,21], and translation [23,24]. The discovery of these specific m6 A processing proteins (i.e., writers, erasers and readers), provided evidence that m6 A modification is a highly regulated, reversible cellular process
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