N6-adenosine-methyltransferase catalytic subunit (METTL3) (METTL3)

N6-adenosine-methyltransferase catalytic subunit (METTL3) is the primary enzyme responsible for depositing N6-methyladenosine (m6A) modifications on eukaryotic messenger RNA (UniProt P35080). As the catalytic core of the m6A methyltransferase complex, it works in conjunction with METTL14 and other regulatory proteins to regulate RNA stability, splicing, and translation efficiency (Nature, 2021, 593(7860):597-601). This epigenetic writer plays a critical role in various biological processes, including embryonic development, cell differentiation, and the circadian clock (PubMed: 24316375). Dysregulation of METTL3 is strongly linked to the pathogenesis of several cancers, most notably acute myeloid leukemia (AML), where it promotes the translation of oncogenes like MYC and BCL2 (Nature, 2021, 593(7860):597-601). Consequently, METTL3 has emerged as a promising therapeutic target, with small-molecule inhibitors like STM2457 and STC-15 currently under investigation to suppress tumor growth by modulating the m6A landscape (Storm Therapeutics; PubMed: 33903481).

Other names

Methyltransferase-like 3MTCBPMT-A70m6A methyltransferaseN6-methyladenosine methyltransferase

Competitive inhibition of the S-adenosyl-L-methionine (SAM) binding pocket within the METTL3 catalytic domain, thereby preventing the transfer of a methyl group to the N6 position of adenosine residues in RNA (Nature, 2021, 593(7860):597-601).