Methyltransferase-like 3 (METTL3) (METTL3)

Methyltransferase-like 3 (METTL3) is the primary catalytic subunit of the N6-methyladenosine (m6A) methyltransferase complex, responsible for the most prevalent internal modification of eukaryotic mRNA (UniProt Q86U44). In hepatocytes, METTL3 acts as a master regulator of metabolic homeostasis by controlling the stability and translation of transcripts involved in lipid and glucose metabolism (PubMed: 30510222). Pathologically, METTL3 is frequently overexpressed in hepatocellular carcinoma (HCC), where it promotes oncogenesis by enhancing the expression of pro-proliferative and epithelial-mesenchymal transition (EMT) factors (PubMed: 28965759). Beyond oncology, its role in hepatocytes extends to metabolic dysfunction-associated steatotic liver disease (MASLD), where it modulates insulin sensitivity and fat accumulation (PubMed: 32066967). Therapeutic strategies currently focus on small-molecule inhibitors like STM2457 that occupy the SAM-binding pocket, offering a novel epigenetic approach to treating liver-related malignancies and metabolic disorders (PubMed: 33903774).

Other names

MTC70MT-A70Methyltransferase-like protein 3N6-adenosine-methyltransferase catalytic subunithMETTL3

Small molecule inhibition of the S-adenosyl-L-methionine (SAM) binding site of the METTL3 catalytic domain, which prevents the installation of N6-methyladenosine (m6A) modifications on target mRNA transcripts, thereby altering their stability and translation (PubMed: 33903774).