The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate

• Published in: PLoS genetics Vol. 7; no. 12; p. e1002403
• Main Authors: Blanco, Sandra, Kurowski, Agata, Nichols, Jennifer, Watt, Fiona M, Benitah, Salvador Aznar, Frye, Michaela
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-12-2011; Public Library of Science (PLoS)
• Subjects: Animals; beta Catenin - metabolism; Biology; Body Weight - genetics; Cell Differentiation - genetics; Cell Differentiation - physiology; Embryonic Development - genetics; Epidermal Cells; Epidermis - metabolism; Hair Follicle - cytology; Hair Follicle - metabolism; Homeostasis; Homeostasis - genetics; Keratinocytes - cytology; Keratinocytes - metabolism; Lymphoid Enhancer-Binding Factor 1 - metabolism; Medical research; Methylation; Methyltransferases; Methyltransferases - genetics; Methyltransferases - metabolism; Mice; Mice, Transgenic; Physiological aspects; Proteins; RNA Processing, Post-Transcriptional - genetics; RNA, Transfer - genetics; RNA, Transfer - metabolism; Rodents; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; United Kingdom; Spain
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002403

Homeostasis of most adult tissues is maintained by balancing stem cell self-renewal and differentiation, but whether post-transcriptional mechanisms can regulate this process is unknown. Here, we identify that an RNA methyltransferase (Misu/Nsun2) is required to balance stem cell self-renewal and differentiation in skin. In the epidermis, this methyltransferase is found in a defined sub-population of hair follicle stem cells poised to undergo lineage commitment, and its depletion results in enhanced quiescence and aberrant stem cell differentiation. Our results reveal that post-transcriptional RNA methylation can play a previously unappreciated role in controlling stem cell fate.