Figure 4.

Suggested roles for NMD in stem cell differentiation. (a) NMD promotes the differentiation of ESCs into the three germ layers, at least partially, by downregulating the mRNA levels of pluripotency genes, like c‐Myc.147 (b) UPF1 promotes the proliferative, undifferentiated state of neuronal stem cells, by inducing the decay of mRNAs encoding proneural factors and proliferation inhibitors. Neuronal differentiation is triggered when a neurogenic signal causes a rapid increase in the levels of the neuronally expressed miR‐128, which downregulates UPF1 mRNA by binding to the 3′ UTR of the UPF1 mRNA, and consequently represses NMD. UPF1 and miR‐128, a part of a self‐reinforcing negative feedback control system, can act as a molecular switch to lock in the different cellular states.148