Exploring the methyl-verse: Dynamic interplay of epigenome and m6A epitranscriptome.

The orchestration of dynamic epigenetic and epitranscriptomic modifications is pivotal for the fine-tuning of gene expression. However, these modifications are traditionally examined independently. Recent compelling studies have disclosed an interesting communication and interplay between m6A RNA methylation (m6A epitranscriptome) and epigenetic modifications, enabling the formation of feedback circuits and cooperative networks. Intriguingly, the interaction between m6A and DNA methylation machinery, coupled with the crosstalk between m6A RNA and histone modifications shape the transcriptional profile and translational efficiency. Moreover, m6A modifications interact also with non-coding RNAs, modulating their stability, abundance, and regulatory functions. In the light of these findings, m6A imprinting acts as a versatile checkpoint, linking epigenetic and epitranscriptomic layers toward a multilayer and time-dependent control of gene expression and cellular homeostasis. The scope of the present review is to decipher the m6A-coordinated circuits with DNA imprinting, chromatin architecture, and non-coding RNAs networks in normal physiology and carcinogenesis. Ultimately, we summarize the development of innovative CRISPR-dCas engineering platforms fused with m6A catalytic components (m6A writers or erasers) to achieve transcript-specific editing of m6A epitranscriptomes that can create new insights in modern RNA therapeutics.