RNAs m6A modification facilitates UVB-induced photoaging

RNA N6-methylation (m⁶A) modification is common in eukaryotic mRNA and has been linked to various physiological disorders, including UVB-induced photoaging. To identify biological differences among photoaging. Three pairs of normal and photoaged skin tissues were collected for m⁶A RNA sequencing assay. Transcriptome profiles showed differential m⁶A methylation modifications in 1365 mRNAs in photoaging skin tissues. Pathway analysis revealed the involvement of cellular stress response and regulation of cell cycle G2/M phase transition in m⁶A-mRNAs. Further experiments validated the differential expression of m⁶A methyltransferases (METTL3 and METTL14) and hypermethylation modification in mRNAs (CENPE, PPM1B and TPM1). <i>In vitro</i> studies demonstrated that increased METTL3 and METTL14 levels promoted m⁶A methylation of CENPE, PPM1B and TPM1 in UVB-induced photoaging cells, and further experiments on mice showed that downregulation of METTL3 and METTL14 reduced m⁶A modifications in CENPE, PPM1B and TPM1, leading to the delayed appearance of photoaging phenotypes, suggesting that these genes could serve as potential therapeutic targets for treating photoaging. Our study characterized key transcriptome changes in photoaging and identified the role of METTL3 and METTL14 in mediating m⁶A modification, resulting in the upregulation of CENPE, PPM1B and TPM1 expression, which may be crucial in UVB-induced photoaging.