METTL1-mediated RNA modification controls hair follicle cycling via a three-gene axis

Researchers publishing in PLOS Genetics have identified a post-transcriptional regulatory mechanism that governs the cyclical growth, regression, and rest phases of hair follicles. The study, led by Xinyan Gan, Qiwen Li, and colleagues, demonstrates that the enzyme METTL1 deposits N7-methylguanosine (m7G) marks on messenger RNAs within hair follicle stem cells, shaping which proteins those cells produce as they commit to specific differentiated identities.

The team mapped a three-component molecular axis — HOXC13, FOXN1, and DSG4 — whose activity is controlled downstream of METTL1-mediated m7G modification. Disrupting this modification pathway impaired normal fate commitment and differentiation of hair follicle stem cells, leading to defects in follicle cycling. The findings add RNA modification to the list of molecular layers — alongside transcription factors and chromatin state — that orchestrate tissue-specific protein synthesis.

The work is primarily of mechanistic interest, clarifying how post-transcriptional control intersects with well-characterised transcriptional networks in a cycling adult tissue. Hair follicle biology is a widely used model for studying adult stem-cell behaviour, tissue renewal, and the coupling of gene expression to cell identity, making the findings relevant to researchers studying RNA biology, stem-cell biology, and epithelial tissue dynamics more broadly.