HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade
Open Access
- 13 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (7), 1-15
- https://doi.org/10.1038/s41419-020-02738-w
Abstract
Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The sequential activation/repression of genes driving cell fate specification is achieved by complex regulatory networks, where transcription factors and noncoding RNAs work in a coordinated manner. Herein, we identify the long noncoding RNA HOTAIRM1 (HOXA Transcript Antisense RNA, Myeloid-Specific 1) as a new player in neuronal differentiation. We demonstrate that the neuronal-enriched HOTAIRM1 isoform epigenetically controls the expression of the proneural transcription factor NEUROGENIN 2 that is key to neuronal fate commitment and critical for brain development. We also show that HOTAIRM1 activity impacts on NEUROGENIN 2 downstream regulatory cascade, thus contributing to the achievement of proper neuronal differentiation timing. Finally, we identify the RNA-binding proteins HNRNPK and FUS as regulators of HOTAIRM1 biogenesis and metabolism. Our findings uncover a new regulatory layer underlying NEUROGENIN 2 transitory expression in neuronal differentiation and reveal a previously unidentified function for the neuronal-induced long noncoding RNA HOTAIRM1.Keywords
Funding Information
- Ministero dell'Istruzione, dell'Università e della Ricerca (Epigen-Epigenomics Flagship Project, PRIN 2017 (PROT. 2017P352Z4, FFABR Anvur 2017)
- Ministero dell'Istruzione, dell'Università e della Ricerca
- Ministero dell'Istruzione, dell'Università e della Ricerca
- Sapienza Università di Roma (RM11916B7A39DCE5, RM11715C7C8176C1)
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