N6-methyladenosine RNA methylation machinery (m6A machinery) (m6A machinery)

The N6-methyladenosine (m6A) RNA methylation machinery is a complex system of proteins that regulates the most abundant internal modification of eukaryotic messenger RNA (mRNA). This machinery consists of "writers" (methyltransferases like METTL3 and METTL14) that install the m6A mark, "erasers" (demethylases like FTO and ALKBH5) that remove it, and "readers" (RNA-binding proteins like the YTH family) that interpret the mark to influence RNA fate (Barbieri & Kouzarides, 2020, Nature Reviews Cancer). By controlling RNA stability, splicing, and translation efficiency, the m6A machinery plays a pivotal role in cellular processes such as differentiation, circadian rhythms, and heat shock responses (Roundtree et al., 2017, Cell). Dysregulation of these components is strongly linked to the pathogenesis of various cancers, particularly acute myeloid leukemia (AML), where METTL3 is often overexpressed to maintain the leukemic state (Yankova et al., 2021, Nature). Therapeutic targeting of the m6A machinery, primarily through small-molecule inhibitors of METTL3 (e.g., STM2457) or FTO (e.g., FB23-2), represents a promising frontier in epitranscriptomic medicine, aiming to restore normal gene expression patterns or induce selective apoptosis in malignant cells (Huang et al., 2019, Cancer Cell).

Other names

m6A regulatorsRNA methylation machinerym6A writers, erasers, and readersEpitranscriptomic machinery

Inhibition of RNA methyltransferases (writers) or RNA demethylases (erasers) to modulate the m6A landscape on mRNA transcripts, thereby altering the stability and translation of oncogenic or tumor-suppressive mRNAs.