Circular RNAs (circRNAs) comprise a large class of conserved non-codingRNAs that regulate a number of biological processes, including transcription, alternative splicing, translation and mRNA decay. circRNAs are enriched in the brain and mammalian cells subjected to neuronal differentiation markedly change their circRNA transcriptomes. Here, we have mapped high-confidence circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and in differentiated glutamatergic neurons and identify hundreds of differentially expressed circRNAs. Among several candidate circRNAs, knockdown of circZNF827 significantly induces expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation. Using Nanostring analyses we demonstrate that among 770 tested genes linked to known neuronal pathways and neuropathological states, knockdown of circZNF827 deregulates expression of several genes including a robust upregulation of neuronal growth factor receptor (NGFR).We show that NGFR becomes transcriptionally upregulated and that this functionally enhances NGF signalling. Our results suggest that circZNF827, although being highly enriched in the cell cytoplasm, can elicit transcriptional changes, which in turn balances proliferation and neuronal differentiation signalling.

No abstract

No abstract

No abstract