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.

HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade / Rea, Jessica; Menci, Valentina; Tollis, Paolo; Santini, Tiziana; Armaos, Alexandros; Garone, Maria Giovanna; Iberite, Federica; Cipriano, Andrea; Tartaglia, Gian Gaetano; Rosa, Alessandro; Ballarino, Monica; Laneve, Pietro; Caffarelli, Elisa. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:7(2020). [10.1038/s41419-020-02738-w]

HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade

Rea, Jessica;Menci, Valentina;Tollis, Paolo;Santini, Tiziana;Garone, Maria Giovanna;Iberite, Federica;Cipriano, Andrea;Tartaglia, Gian Gaetano;Rosa, Alessandro;Ballarino, Monica;Laneve, Pietro
Penultimo
;
Caffarelli, Elisa
Ultimo
2020

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.
2020
long noncoding RNA; Neuronal differentiation; Growth Arrest Specific Transcript 5; Small Nucleolar RNA
01 Pubblicazione su rivista::01a Articolo in rivista
HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade / Rea, Jessica; Menci, Valentina; Tollis, Paolo; Santini, Tiziana; Armaos, Alexandros; Garone, Maria Giovanna; Iberite, Federica; Cipriano, Andrea; Tartaglia, Gian Gaetano; Rosa, Alessandro; Ballarino, Monica; Laneve, Pietro; Caffarelli, Elisa. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 11:7(2020). [10.1038/s41419-020-02738-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1429819
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