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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reciprocal actions of REST and a microRNA promote neuronal identity
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Reciprocal actions of REST and a microRNA promote neuronal identity

机译：REST和microRNA的相互作用促进神经元身份

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摘要

MicroRNAs (miRNAs) are implicated in both tissue differentiation and maintenance of tissue identity. In most cases, however, the mechanisms underlying their regulation are not known. One brain-specific miRNA, miR-124a, decreases the levels of hundreds of nonneuronal transcripts, such that its introduction into HeLa cells promotes a neuronal-like mRNA profile. The transcriptional repres-sor, RE1 silencing transcription factor (REST), has a reciprocal activity, inhibiting the expression of neuronal genes in nonneuronal cells. Here, we show that REST regulates the expression of a family of miRNAs, including brain-specific miR-124a. In nonneuronal cells and neural progenitors, REST inhibits miR-124a expression, allowing the persistence of nonneuronal transcripts. As progenitors differentiate into mature neurons, REST leaves miR-124a gene loci, and nonneuronal transcripts are degraded selectively. Thus, the combined transcriptional and posttranscriptional consequences of REST action maximize the contrast between neuronal and nonneuronal cell phenotypes.
机译：MicroRNA（miRNA）与组织分化和组织同一性的维持有关。但是，在大多数情况下，尚不清楚其调控的机制。一种大脑特异性的miRNA miR-124a降低了数百种非神经元转录本的水平，因此将其引入HeLa细胞可促进神经元样mRNA谱。转录代表RE1沉默转录因子（REST）具有交互作用，可抑制非神经元细胞中神经元基因的表达。在这里，我们显示REST调节miRNA家族的表达，包括大脑特异性miR-124a。在非神经元细胞和神经祖细胞中，REST抑制miR-124a表达，从而使非神经元转录本得以持久存在。随着祖细胞分化成成熟的神经元，REST离开了miR-124a基因位点，非神经元转录物被选择性降解。因此，REST作用的组合转录和转录后结果使神经元和非神经元细胞表型之间的对比度最大化。

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