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

• Published in: Cell death & disease 2020-07, Vol.11 (7), p.527-527, Article 527
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 631/136/142; 631/337/176/2016; 631/337/384/2568; 631/378/368; 631/45/475; Antibodies; Antisense RNA; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Differentiation - physiology; Cell fate; Cell Line, Tumor; Epigenesis, Genetic; Gene expression; Gene Silencing; Heterogeneous-Nuclear Ribonucleoprotein K - genetics; Heterogeneous-Nuclear Ribonucleoprotein K - metabolism; Humans; Immunology; Life Sciences; MicroRNAs - genetics; MicroRNAs - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurogenins; Neurons - cytology; Neurons - metabolism; Proteomics - methods; Ribonucleic acid; RNA; RNA-binding protein; RNA-Binding Protein FUS - genetics; RNA-Binding Protein FUS - metabolism; Transcription activation; Transcription factors; Transcription Factors - metabolism; Transfection
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-02738-w

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.