A conserved microRNA/NMD regulatory circuit controls gene expression.

Nonsense-mediated decay (NMD) is a RNA surveillance pathway that degrades subsets of normal and aberrant mRNAs. Mutations that perturb NMD cause neurological disorders in humans, suggesting that NMD has roles in the brain. Recently, it was shown that NMD is repressed during neural development to allow for the stabilization of NMD mRNA targets. The repression of NMD during development is mediated by a neuron-expressed microRNA, miR-128, which participates in a highly conserved regulatory circuit. miR-128 is induced in differentiating neuronal cells and during brain development, leading to repressed NMD and the consequent upregulation of batteries of mRNAs encoding proteins important for neuron differentiation and function. Together with other results, this suggests the existence of a complex network linking the microRNA and NMD pathways that induce cell-specific transcripts. In this point-of-view article, we will discuss the repercussions of this discovery for neuronal development, brain function and disease.