RNAs m⁶A modification facilitates UVB-induced photoaging

Area of Science:

• Molecular Biology
• Dermatology
• Epigenetics

Background:

• RNA N6-methylation (m⁶A) is a prevalent mRNA modification in eukaryotes.
• m⁶A modification is implicated in various physiological processes and diseases, including skin photoaging.
• UVB radiation is a significant factor contributing to skin aging.

Purpose of the Study:

• To investigate the role of m⁶A modification in UVB-induced photoaging.
• To identify specific genes and pathways affected by m⁶A changes in photoaged skin.
• To explore potential therapeutic targets for photoaging based on m⁶A regulation.

Main Methods:

• m⁶A RNA sequencing was performed on normal and photoaged human skin tissues.
• Bioinformatic analysis identified differentially methylated mRNAs and associated pathways.
• Gene expression analysis, in vitro cell studies, and in vivo mouse models were used to validate findings.

Main Results:

• 1365 mRNAs exhibited differential m⁶A methylation in photoaged skin.
• Pathways related to cellular stress and G2/M cell cycle transition were enriched.
• METTL3 and METTL14 levels were altered, affecting m⁶A methylation of CENPE, PPM1B, and TPM1, which were upregulated in photoaging.

Conclusions:

• METTL3 and METTL14 play a crucial role in mediating m⁶A modifications in UVB-induced photoaging.
• Upregulation of CENPE, PPM1B, and TPM1 via m⁶A modification contributes to photoaging phenotypes.
• Targeting METTL3, METTL14, or their downstream targets may offer therapeutic strategies for photoaging.