RNA degradation drives stem cell differentiation.

The mechanisms by which multi-potent stem cells switch their program to become functional differentiated cells have intrigued biologists for decades. Most focus has been on transcriptional pathways, but whether they have sufficient dynamic range to cause discrete shifts in cell state is not clear. Because the steady-state level of RNAs is also dictated by their decay rate, an attractive possibility is that specific RNA decay mechanisms also have a role in promoting differentiation mechanisms. In this issue of The EMBO Journal, Li et al (2015) obtained evidence that a highly conserved RNA degradation pathway called nonsense-mediated RNA decay (NMD) is critical for the differentiation of embryonic stem (ES) cells.