Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China.
Cell Biochem Funct. 2011 Jun;29(4):279-86. doi: 10.1002/cbf.1747. Epub 2011 Mar 31.
MicroRNA (miRNAs) are short non-coding RNA molecules that downregulate gene expression at post-transcriptional level. miRNAs are post-transcriptional regulators of gene expression important for neuron development and function. This report demonstrated that a putative and chemically synthesized miRNA rno-mir-541 played an important role in the neuron development. Differentiation of PC12 cells with nerve growth factor (NGF) is associated with neurite outgrowth, a process that involves upregulation of Synapsin I. We predicted, detected and assessed the expression levels of a number of possible miRNAs for synapsin I in rats and our outcomes showed that rno-mir-541 was associated with rat synapsin I expression. miR-541, a brain specific miRNA, plays an important role in repressing neurite extension in cultured PC12 neurons. The neurites of PC12 cells was shortened drasticly as a result of the overexpression of rno-mir-541. In contrast, the neurites of PC12 cell developed well after the knockdown of rno-mir-541 by RNA interference. Our study showed that rno-mir-541 played an important role in neuron-cell proliferation and neurite outgrowth through suppressing the expression of its target gene synapsin I. Furthermore, the introduction of NGF causes downregulation of miR-541, de-repression of its target, Synapsin-I and allows for neuritogenesis. Thus, miR-541 functions in neuronal precursors as an endogenous conditional component between NGF and Synapsin-I.
微小 RNA(miRNAs)是一种短的非编码 RNA 分子,可在转录后水平下调基因表达。miRNAs 是基因表达的转录后调节剂,对于神经元的发育和功能很重要。本报告表明,一种假定的化学合成 miRNA rno-mir-541 在神经元发育中发挥重要作用。用神经生长因子(NGF)分化 PC12 细胞与轴突生长有关,这一过程涉及突触素 I 的上调。我们预测、检测并评估了大鼠中与突触素 I 相关的许多可能的 miRNAs 的表达水平,结果表明 rno-mir-541 与大鼠突触素 I 的表达有关。miR-541 是一种大脑特异性 miRNA,在抑制培养的 PC12 神经元中的轴突延伸中发挥重要作用。rno-mir-541 的过表达导致 PC12 细胞的轴突急剧缩短。相反,rno-mir-541 的 RNA 干扰敲低后,PC12 细胞的轴突发育良好。我们的研究表明,rno-mir-541 通过抑制其靶基因突触素 I 的表达,在神经元-细胞增殖和轴突生长中发挥重要作用。此外,NGF 的引入导致 miR-541 的下调、其靶基因突触素 I 的去抑制,从而允许神经发生。因此,miR-541 在神经元前体中作为 NGF 和突触素 I 之间的内源性条件成分发挥作用。