PT  - JOURNAL ARTICLE
AU  - Anne Kruse Hollensen
AU  - Henriette Sylvain Thomsen
AU  - Marta Lloret-Llinares
AU  - Andreas Bjerregaard Kamstrup
AU  - Jacob Malthe Jensen
AU  - Majbritt Luckmann
AU  - Nanna Birkmose
AU  - Johan Palmfeldt
AU  - Torben Heick Jensen
AU  - Thomas Birkballe Hansen
AU  - Christian Kroun Damgaard
TI  - circZNF827 nucleates a transcription inhibitory complex to balance neuronal differentiation
AID  - 10.1101/791798
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 791798
4099  - http://biorxiv.org/content/early/2020/05/15/791798.short
4100  - http://biorxiv.org/content/early/2020/05/15/791798.full
AB  - Circular RNAs are important for many cellular processes but their mechanisms of action remain poorly understood. Here, we map circRNA inventories of mouse embryonic stem cells, neuronal progenitor cells and differentiated neurons and identify hundreds of highly expressed circRNAs. By screening several candidate circRNAs for a potential function in neuronal differentiation, we find that circZNF827 represses expression of key neuronal markers, suggesting that this molecule negatively regulates neuronal differentiation. Among 760 tested genes linked to known neuronal pathways, knockdown of circZNF827 deregulates expression of numerous genes including nerve growth factor receptor (NGFR), which becomes transcriptionally upregulated to enhance NGF signalling. We identify a circZNF827-nucleated transcription-repressive complex containing hnRNP-K/L proteins and show that knockdown of these factors strongly augments NGFR regulation. Finally, we show that ZNF827 protein is part of the mRNP complex, suggesting a functional co-evolution of a circRNA and the protein encoded by its linear pre-mRNA host.Competing Interest StatementThe authors have declared no competing interest.