In specific niches of the adult mammalian brain, neural progenitor cells (aNPCs) ensure lifelong neurogenesis. Proper regulation of this process entails important implications for brain plasticity and health. We report that Piwil2 (Mili) and PIWI-interacting RNAs (piRNAs) are abundantly expressed in aNPCs but depleted in their progeny in the adult mouse hippocampus. Loss of function of the piRNA pathway in aNPCs inhibited neurogenesis and increased reactive gliogenesis in vivo and in vitro. PiRNA pathway depletion in cultured aNPCs increased levels of 5S ribosomal RNA, transfer RNAs and mRNAs encoding regulators of translation, resulting in higher polyribosome density and protein synthesis upon differentiation. We propose that the piRNA pathway sustains adult neurogenesis by repressing translation in aNPCs.
bioRxiv Subject Collection: Neuroscience