Methyltransferase-like protein 3–Methyltransferase-like protein 14 complex (METTL3–METTL14)

The **Methyltransferase-like protein 3–Methyltransferase-like protein 14 complex** (METTL3–METTL14) is a core nuclear enzyme complex responsible for catalyzing the methylation of adenosine residues at the N6 position (m^6^A) in various RNA species, most notably messenger RNA (mRNA)[1][3][5][8]. METTL3 functions as the catalytically active subunit, utilizing S-adenosylmethionine (SAM) as the methyl donor, while METTL14 forms a stable heterodimer with METTL3, supporting structural integrity and substrate RNA recognition but lacking catalytic activity[1][2][6][7][9]. This complex, frequently associated with regulatory subunits such as WTAP, is essential for m^6^A "writer" function and modulates key RNA metabolic processes including alternative splicing, translation, and decay, with broad impacts on gene expression, cell fate, and disease pathogenesis[9]. Dysregulation or mutation in METTL3 or METTL14 has been implicated in oncogenesis and other diseases, making the complex a therapeutic target in drug development, especially in cancer and certain developmental or neurological conditions[1][9]. Small-molecule inhibitors of METTL3 are in preclinical or early clinical development and act predominantly by interfering with its SAM-binding site, thereby suppressing m^6^A installation and affecting RNA function[8].

Other names

m^6^A writer complexN6-methyladenosine methyltransferase complexMETTL3/14 complex

Competitive inhibition of the S-adenosylmethionine (SAM) binding site (for inhibitors) - Disruption of m^6^A installation on mRNA, altering transcript fate and expression