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

Neuronal differentiation is a timely and spatially regulated process orchestrated by a synergy between transcription factors and noncoding RNAs. Here we demonstrate that the long noncoding RNA HOTAIRM1 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.