N6-methyladenosine (m6A)

N6-methyladenosine (m6A) is the most abundant and well-characterized internal post-transcriptional modification in eukaryotic messenger RNA (mRNA). This dynamic epitranscriptomic mark is installed by a "writer" complex (primarily METTL3 and METTL14), removed by "eraser" enzymes (such as FTO and ALKBH5), and interpreted by "reader" proteins (like the YTH family). m6A modification plays a critical role in regulating mRNA metabolism, including splicing, nuclear export, stability, and translation efficiency. Dysregulation of the m6A landscape is heavily implicated in various human diseases, most notably in acute myeloid leukemia (AML) and various solid tumors, where it often stabilizes oncogenic transcripts like MYC and BCL2. Therapeutic strategies currently focus on small molecule inhibitors of m6A writers and erasers, with compounds like the METTL3 inhibitor STM2457 and the FTO inhibitor Bisantrene showing promise in preclinical and early clinical studies. Beyond oncology, m6A is also being explored for its roles in obesity, neurodegeneration, and viral infection, making it a versatile target for epitranscriptomic therapy.

Other names

6-methyladenosinem6Am6A RNA methylationN6-methyladenosine modificationEpitranscriptomic m6A markN6-methyladenosine modified RNA

Inhibition of m6A methyltransferases (writers) or demethylases (erasers) to modulate the stability, splicing, and translation of target oncogenic or tumor-suppressor transcripts.