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

PLoS Genet. 2011 Dec;7(12):e1002403. doi: 10.1371/journal.pgen.1002403. Epub 2011 Dec 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / genetics
  • Cell Differentiation / genetics*
  • Cell Differentiation / physiology
  • Embryonic Development / genetics
  • Epidermal Cells
  • Epidermis / metabolism*
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Homeostasis / genetics
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Methylation
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • Mice
  • Mice, Transgenic
  • RNA Processing, Post-Transcriptional / genetics
  • RNA, Transfer / genetics
  • RNA, Transfer / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • beta Catenin / metabolism

Substances

  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • beta Catenin
  • RNA, Transfer
  • Methyltransferases
  • Misu protein, mouse