Modulation of mA RNA modification by DAP3 in cancer cells.

N-methyladenosine (mA) RNA methylation is a prevalent RNA modification that significantly impacts RNA metabolism and cancer development. Maintaining the global mA levels in cancer cells relies on RNA accessibility to methyltransferases and the availability of the methyl donor S-adenosylmethionine (SAM). Here, we reveal that death associated protein 3 (DAP3) plays a crucial role in preserving mA levels through two distinct mechanisms. First, although DAP3 is not a component of the mA writer complex, it directly binds to mA target regions, thereby facilitating METTL3 binding. Second, DAP3 promotes 's last intron splicing, increasing MAT2A protein, cellular SAM, and mA levels. Silencing DAP3 hinders tumorigenesis, which can be rescued by MAT2A overexpression. This evidence suggests DAP3's role in tumorigenesis, partly through mA regulation. Our findings unveil DAP3's complex role as an RNA-binding protein and tumor promoter, impacting RNA processing, splicing, and mA modification in cancer transcriptomes.