The RNA–Methyltransferase Misu (NSun2) Poises Epidermal Stem Cells to Differentiate

Abstract

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. We demonstrate that the RNA methyltransferase activity of Misu/NSun2 is required for the proper maintenance of the epidermal differentiation program, and thus post-transcriptional mechanisms are involved in controlling the balance between stem cell self-renewal and differentiation.