Long Non-coding RNA T-UCstem1 Controls Progenitor Proliferation and Neurogenesis in the Postnatal Mouse Olfactory Bulb through Interaction with miR-9

长链非编码 RNA T-UCstem1 通过与 miR-9 相互作用控制出生后小鼠嗅球中的祖细胞增殖和神经发生

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作者:Emilia Pascale, Christophe Beclin, Alessandro Fiorenzano, Gennaro Andolfi, Andrea Erni, Sandro De Falco, Gabriella Minchiotti, Harold Cremer, Annalisa Fico

Abstract

Neural stem cell populations generate a wide spectrum of neuronal and glial cell types in a highly ordered fashion. MicroRNAs are essential regulators of this process. T-UCstem1 is a long non-coding RNA containing an ultraconserved element, and in vitro analyses in pluripotent stem cells provided evidence that it regulates the balance between proliferation and differentiation. Here we investigate the in vivo function of T-UCstem1. We show that T-UCstem1 is expressed in the forebrain neurogenic lineage that generates interneurons for the postnatal olfactory bulb. Gain of function in neural stem cells increased progenitor proliferation at the expense of neuron production, whereas knockdown had the opposite effect. This regulatory function is mediated by its interaction with miR-9-3p and miR-9-5p. Based thereon, we propose a mechanistic model for the role of T-UCstem1 in the dynamic regulation of neural progenitor proliferation during neurogenesis.

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