A small modulatory dsRNA specifies the fate of adult neural stem cells
A small modulatory dsRNA specifies the fate of adult neural stem cells
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DOI：
10.1016/s0092-8674(04)00248-x
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发表时间：
2004-03-19
期刊：
影响因子：
64.5
通讯作者：
Gage, FH
中科院分区：
文献类型：
--
作者：
Kuwabara, T;Hsieh, J;Gage, FH
发现调节神经元特异性基因表达的分子机制仍然是中枢神经系统研究的核心挑战。在这里，我们报告小的非编码双链 [ds) RNA 在介导神经元分化中发挥着关键作用。该 dsRNA 定义的序列是 NRSE/RE1，它被 NRSF/REST 识别，主要作为限制神经元基因表达到神经元的负转录调节因子。 NRSE dsRNA 可以通过与 NRSF/REST 转录机制的相互作用触发神经元特异性基因的基因表达，从而导致具有被 NRSF/REST 沉默的神经元特异性基因的神经干细胞转变为可以表达神经元基因的具有神经元身份的细胞。作用机制似乎是通过 dsRNA/蛋白质相互作用介导的，而不是通过 siRNA 或 miRNA。小调节 dsRNA (smRNA) 的发现扩展了非编码 RNA 作为转录和转录后水平细胞行为关键调节因子的重要贡献。
Discovering the molecular mechanisms that regulate neuron-specific gene expression remains a central challenge for CNS research. Here, we report that small, noncoding double-stranded [ds) RNAs play a critical role in mediating neuronal differentiation. The sequence defined by this dsRNA is NRSE/RE1, which is recognized by NRSF/REST, known primarily as a negative transcriptional regulator that restricts neuronal gene expression to neurons. The NRSE dsRNA can trigger gene expression of neuron-specific genes through interaction with NRSF/REST transcriptional machinery, resulting in the transition from neural stem cells with neuron-specific genes silenced by NRSF/REST into cells with neuronal identity that can express neuronal genes. The mechanism of action appears to be mediated through a dsRNA/protein interaction, rather than through siRNA or miRNA. The discovery of small modulatory dsRNAs (smRNAs) extends the important contribution of noncoding RNAs as key regulators of cell behavior at both transcriptional and posttranscriptional levels.