Division of Molecular Biology, Biomedical Center Munich, Ludwig-Maximilians-University, Munich, Germany.
Division of Metabolic Biochemistry, Faculty of Medicine, Biomedical Center Munich (BMC), Ludwig-Maximilians-Universität München, Munich, Germany.
Life Sci Alliance. 2022 Jun 10;5(10). doi: 10.26508/lsa.202201504. Print 2022 Oct.
The evolution of brain complexity correlates with an increased expression of long, noncoding (lnc) RNAs in neural tissues. Although prominent examples illustrate the potential of lncRNAs to scaffold and target epigenetic regulators to chromatin loci, only few cases have been described to function during brain development. We present a first functional characterization of the lncRNA , which we term for "RNA upstream of Slitrk3." The gene is well conserved in mammals by sequence and synteny next to the neurodevelopmental gene Slitrk3. is exclusively expressed in neural cells and its expression increases during neuronal differentiation of mouse embryonic cortical neural stem cells. Depletion of locks neuronal precursors in an intermediate state towards neuronal differentiation resulting in arrested cell cycle and increased apoptosis. associates with chromatin in the vicinity of genes involved in neurogenesis, most of which change their expression upon depletion. The identification of a range of epigenetic regulators as specific interactors suggests that the lncRNA may mediate gene activation and repression in a highly context-dependent manner.
大脑复杂性的进化与神经组织中长非编码 (lnc) RNA 的表达增加有关。尽管有突出的例子说明了 lncRNA 作为支架和靶向表观遗传调节剂到染色质位置的潜力，但在大脑发育过程中仅有少数情况被描述为具有功能。我们首次对 lncRNA 进行了功能表征，我们将其命名为“Slitrk3 上游 RNA”。该基因在哺乳动物中通过序列和基因座的同线性得到很好的保守，紧邻神经发育基因 Slitrk3。在小鼠胚胎皮质神经干细胞的神经元分化过程中， 仅在神经细胞中表达，其表达增加。 耗尽会使神经元前体锁定在向神经元分化的中间状态，导致细胞周期停滞和凋亡增加。 与参与神经发生的基因附近的染色质相关联，其中大多数基因在 耗尽时改变其表达。一系列表观遗传调节剂被鉴定为特定的 相互作用因子，这表明该 lncRNA 可能以高度依赖上下文的方式介导基因的激活和抑制。
