Fig. 4.

Regulation of RNA m6A modification on ferroptosis. m6A modification is a reversible and dynamic process mediated by methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). All of these three components are implicated in the splicing, translation, and stability of mRNA. RNA m6A modification can induce or inhibit ferroptosis via regulating the expression of ferroptosis-related targets. For instance, WTAP/YTHDF1 can increase the stability of NRF2, which can activate the transcriptions of SLC7A11 and consequently inhibit ferroptosis. miR-4443 inhibited cisplatin-induced ferroptosis of tumor cells by decreasing the expression level of METTL3 and increasing the level of FSP1. YTHDC2 can promote the degradation of SLC3A2 mRNA and induce ferroptosis. METTL3/IGF2BP1 pathway can stabilize SLC7A11 mRNA and NKAP/SFPQ pathway can promote its maturation, both of which inhibit ferroptosis. The FTO and METTL14/YTHDF2 axes accelerate its degradation, thereby inducing ferroptosis. Moreover, NETs-induced upregulation of METTL3 acts through the TLR9/MyD88/NF-κB signaling pathway in alveolar epithelial cells, which in turn induces ferroptosis in alveolar epithelial cells. In breast cancer, decreased levels of METTL16 expression lead to decreased levels of m6A methylation of GPX4 RNA and ferroptosis. This figure was created with BioRender.com