Reciprocal actions of REST and a microRNA promote neuronal identity
Reciprocal actions of REST and a microRNA promote neuronal identity
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DOI：
10.1073/pnas.0511041103
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发表时间：
2006-02-14
影响因子：
11.1
通讯作者：
Mandel, G
中科院分区：
文献类型：
--
作者：
Conaco, C;Otto, S;Mandel, G
MicroRNAs （miRNAs）涉及组织分化和组织身份的维持。然而，在大多数情况下，其调控机制尚不清楚。一种脑特异性miRNA miR-124a降低了数百种非神经元转录物的水平，因此将其引入HeLa细胞可促进神经元样mRNA谱。转录抑制因子RE1沉默转录因子（REST）具有互反活性，可抑制非神经元细胞中神经元基因的表达。在这里，我们发现REST调节一系列mirna的表达，包括脑特异性miR-124a。在非神经元细胞和神经祖细胞中，REST抑制miR-124a的表达，允许非神经元转录物的持续存在。当祖细胞分化为成熟神经元时，REST会留下miR-124a基因位点，非神经元转录物被选择性地降解。因此，REST作用的联合转录和转录后后果最大限度地提高了神经元和非神经元细胞表型之间的差异。
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 repressor, 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.