Non-canonical post-transcriptional RNA regulation of neural stem cell potential.

Abstract

Adult brain structures and complexity emerge from a single layer of neuroepithelial cells that early during the development give rise to neural stem cells (NSCs). NSCs persist in restricted regions of the postnatal brain where they support neurogenesis throughout life thus allowing brain plasticity and adaptation. NSC regulation involves a precise coordination of intrinsic and extrinsic mechanisms that finely modulate the neurogenic process. Here we will discuss new mechanisms of post-transcriptional gene regulation that act in the embryonic and adult brain to regulate NSC maintenance and differentiation. In our recent work we found that the RNAaseIII Drosha not only regulates microRNA production, but also directly affects the stability of mRNAs and thereby controls proteome composition. This non-canonical (miRNA-independent) function of Drosha is central in the maintenance and fate choices made by adult hippocampal NSCs in the healthy brain. We found that Drosha targets the mRNA of the gliogenic transcription factor Nuclear Factor I/B and thereby blocks its expression in the NSCs. In the absence of Drosha, NSCs aberrantly differentiate into oligodendrocytes and are lost leading to an impairment of neurogenesis. Overall these findings reveal an unprecedented Drosha-mediated post-transcriptional mechanism for the regulation of hippocampal NSC potential.