Laboratory of Pharmacology, Department of Health Sciences, University of Milan , Milan , Italy.
Pediatric Clinical Research Center Fondazione "Romeo ed Enrica Invernizzi", University of Milan , Milan , Italy.
RNA Biol. 2019 Oct;16(10):1471-1485. doi: 10.1080/15476286.2019.1637698. Epub 2019 Jul 26.
LncRNAs play crucial roles in cellular processes and their regulatory effects in the adult brain and neural stem cells (NSCs) remain to be entirely characterized. We report that 10 lncRNAs (LincENC1, FABL, lincp21, HAUNT, PERIL, lincBRN1a, lincBRN1b, HOTTIP, TUG1 and FENDRR) are expressed during murine NSCs differentiation and interact with the RNA-binding protein ELAVL1/HuR. Furthermore, we characterize the function of two of the deregulated lncRNAs, lincBRN1a and lincBRN1b, during NSCs' differentiation. Their inhibition leads to the induction of differentiation, with a concomitant decrease in stemness and an increase in neuronal markers, indicating that they exert key functions in neuronal cells differentiation. Furthermore, we describe here that HuR regulates their half-life, suggesting their synergic role in the differentiation process. We also identify six human homologs (PANTR1, TUG1, HOTTIP, TP53COR, ELDRR and FENDRR) of the mentioned 10 lncRNAs and we report their deregulation during human iPSCs differentiation into neurons. In conclusion, our results strongly indicate a key synergic role for lncRNAs and HuR in neuronal stem cells fate.
lncRNAs 在细胞过程中发挥着关键作用,但其在成年大脑和神经干细胞(NSCs)中的调节作用仍有待全面描述。我们报告了 10 个 lncRNAs(LincENC1、FABL、lincp21、HAUNT、PERIL、lincBRN1a、lincBRN1b、HOTTIP、TUG1 和 FENDRR)在小鼠 NSCs 分化过程中表达,并与 RNA 结合蛋白 ELAVL1/HuR 相互作用。此外,我们还研究了两个失调 lncRNAs(lincBRN1a 和 lincBRN1b)在 NSCs 分化过程中的功能。抑制它们会诱导分化,同时降低干细胞特性并增加神经元标志物,表明它们在神经元细胞分化中发挥关键功能。此外,我们在这里描述 HuR 调节它们的半衰期,表明它们在分化过程中具有协同作用。我们还鉴定了所提到的 10 个 lncRNAs 中的 6 个人类同源物(PANTR1、TUG1、HOTTIP、TP53COR、ELDRR 和 FENDRR),并报告了它们在人类 iPSCs 分化为神经元过程中的失调。总之,我们的结果强烈表明 lncRNAs 和 HuR 在神经干细胞命运中具有关键的协同作用。