RNA methyltransferase (RNMT) (RNMT)

RNA methyltransferases (RNMTs) are a diverse superfamily of enzymes that catalyze the transfer of a methyl group from a donor, usually S-adenosyl-L-methionine (SAM), to specific positions on RNA molecules including mRNA, tRNA, and rRNA (Barbieri & Kouzarides, Nature Reviews Cancer, 2020). These enzymes function as "writers" in the epitranscriptomic landscape, installing modifications such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) that regulate RNA stability, splicing, and translation (Yankova et al., Nature, 2021). Dysregulation of RNA methyltransferases, particularly the METTL3/METTL14 complex, has been strongly implicated in the pathogenesis of various cancers, most notably acute myeloid leukemia (AML), where they maintain the survival of leukemic stem cells (Yankova et al., Nature, 2021; Cully, Nature Reviews Drug Discovery, 2021). Consequently, they have emerged as high-priority therapeutic targets, with small-molecule inhibitors like STM2457 demonstrating potent anti-tumor activity in preclinical models by reducing m6A levels and inducing differentiation or apoptosis in malignant cells (Yankova et al., Nature, 2021). Beyond oncology, these enzymes are also investigated for their roles in viral replication and neurological disorders, though therapeutic development in these areas is still in early stages (UniProt, 2024; Barbieri & Kouzarides, 2020).

Other names

RNA-specific methyltransferase (UniProt)RNA MTase (UniProt)Epitranscriptomic writer (Barbieri & Kouzarides, 2020)RNA methylase (PubMed)

Inhibition of the catalytic activity of RNA methyltransferases, typically by competing with the methyl donor S-adenosyl-L-methionine (SAM) or the RNA substrate, thereby modulating the levels of specific RNA modifications such as m6A (Yankova et al., Nature, 2021; Cully, Nature Reviews Drug Discovery, 2021).