mRNA N6-adenosine-methyltransferase complex (METTL3-METTL14 complex (or METTL3-14))

The mRNA N6-adenosine-methyltransferase complex (commonly called the m6A writer complex) catalyzes the addition of a methyl group to the N6 position of adenosine residues on messenger RNA (mRNA), generating N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes[2][3][4][7]. The core of this complex consists of the proteins METTL3 (the catalytic subunit) and METTL14 (an obligate scaffolding subunit), sometimes with additional regulatory proteins such as WTAP[6][7]. m6A deposition is essential for proper regulation of mRNA splicing, translation, stability, and nuclear export and has broad biological significance for cellular differentiation, proliferation, development, and various stress responses[3][6][7]. Dysregulation of m6A writers is implicated in a variety of diseases, especially cancer, but also in metabolic, infectious, and developmental disorders[2][3][4][6][7]. METTL3 is viewed as a promising therapeutic target and candidate biomarker in multiple cancer types. Selective chemical inhibitors of METTL3, like STM2457, are being evaluated in preclinical studies[2]. However, due to the complex and global role of m6A in transcript regulation, manipulating this target may present risks of off-target or wide-ranging systemic effects. Caveat: The term "mRNA methyltransferase" can also refer to several other mRNA-modifying enzymes, such as those performing cap methylation (e.g., RNMT) or 2’O-methylation, but in the current literature and disease context, it most commonly and specifically refers to the METTL3-METTL14 complex responsible for m6A installation[5][9]. If instead referring to viral or 5’ cap methyltransferases, adjust accordingly. The above information provides the most disease-relevant, canonical usage for "mRNA methyltransferase" as currently accepted.

Other names

mRNA methyltransferasem6A RNA methyltransferaseN6-methyladenosine methyltransferaseMETTL3-METTL14 complexm6A writer complexMETTL3/METTL14 (core proteins)METTL3 (sometimes used to refer to full complex in literature)

Inhibition of m6A installation on mRNA (e.g., by inhibiting METTL3, m6A modification—and thus downstream mRNA fate and translation—is reduced); Modulation of epitranscriptomic signaling pathways (altering mRNA processing, stability, or translation for therapeutic effect)