Neurogenin 2 expression is regulated by the long noncoding RNA HOTAIRM1 during in vitro neuronal differentiation

Neurons derive from neural progenitor cells whose differentiation occurs in two distinct steps, each one involving specific regulatory cascades. The initial production of neuronal precursors, cells already committed to a neuronal fate, is followed by the formation of differentiated cell types that acquire and maintain their identity. The molecular mechanisms underlying these timely-regulated steps are object of intense studies. A prime role in this process is played by proneural genes, regarded as key regulators of neurogenesis. They function by activating neuronal differentiation gene cascades, inhibiting glial cell fates and regulating cell cycle. The proneural transcription factor Neurogenin 2 (Ngn2) is pivotal in the decision between stem cell self-renewal and differentiation. Its expression is tightly regulated during differentiation and even subtle alterations of Ngn2 levels could affect cell fate. Ngn2 is activated in neuronal precursors to be repressed in post-mitotic cells through a still unknown mechanism. We identified a role in this process for the long noncoding RNA HOTAIRM1, so far described as a regulator of the HOXA genes. We characterized the neuronal isoform of this RNA and found that the nuclear counterpart controls Ngn2 expression at the epigenetic level.