N6-methyladenosine [3, 13] (m6A [3, 13])

N6-methyladenosine (m6A) is the most prevalent and abundant internal modification in eukaryotic messenger RNA (mRNA), serving as a key regulatory node in the field of epitranscriptomics [3, 13]. It is dynamically and reversibly regulated by a suite of proteins: "writers" (methyltransferases like METTL3 and METTL14) that install the mark, "erasers" (demethylases like FTO and ALKBH5) that remove it, and "readers" (such as YTH domain proteins) that recognize and execute its biological effects [1, 4, 7]. m6A influences nearly every stage of the RNA life cycle, including splicing, nuclear export, translation efficiency, and stability [6, 11, 12]. Dysregulation of m6A is implicated in a wide range of human diseases, particularly in oncology where it drives the progression of acute myeloid leukemia (AML) and various solid tumors [5, 8, 9]. Therapeutic intervention typically involves small-molecule inhibitors targeting the writers or erasers to restore homeostatic m6A levels [1, 4, 5]. However, because m6A is essential for normal cellular function, targeting this pathway requires careful consideration of potential systemic toxicity and off-target effects on the broader transcriptome [4, 11].

Other names

6-methyladenosine [3]m6A RNA modification [1, 5]N6-methyl-adenosine [3, 5]m6A [3, 13]

Modulation of m6A levels through inhibition of methyltransferase writers or demethylase erasers [1, 4, 5].