Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2
Intronic miR-26b controls neuronal differentiation by repressing its host transcript, ctdsp2
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DOI：
10.1101/gad.177774.111
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发表时间：
2012-01-01
影响因子：
10.5
通讯作者：
Fischer, Utz
中科院分区：
文献类型：
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作者：
Dill, Holger;Linder, Bastian;Fischer, Utz
神经干细胞(NSCs)向神经元分化需要激活抑制因子1(Re1)沉默转录因子(REST)/神经元限制性沉默因子(NRSF)蛋白复合体控制的基因。REST/NRSF的重要成分是磷酸酶(称为RNA聚合酶II C端域小磷酸酶[CTDSPs])，它抑制RNA聚合酶II和抑制神经干细胞中神经元基因的表达。CTDSP控制的基因的激活是神经发生所必需的，但这是如何实现的还不完全清楚。在这里，我们表明ctdsp2是miR-26b的靶标，miR-26b是一种编码在ctdsp2初级转录本的内含子中的microRNA。这种内在的负反馈环在NSCs中是不活跃的，因为miR-26b的生物发生在前体水平被抑制。成熟miR-26b的产生在神经发生过程中被激活，它抑制Ctdsp2蛋白的表达，是体内神经细胞分化所必需的。
Differentiation of neural stem cells (NSCs) to neurons requires the activation of genes controlled by the repressor element 1 (RE1) silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) protein complex. Important components of REST/NRSF are phosphatases (termed RNA polymerase II C-terminal domain small phosphatases [CTDSPs]) that inhibit RNA polymerase II and suppress neuronal gene expression in NSCs. Activation of genes controlled by CTDSPs is required for neurogenesis, but how this is achieved is not fully understood. Here we show that ctdsp2 is a target of miR-26b, a microRNA that is encoded in an intron of the ctdsp2 primary transcript. This intrinsic negative feedback loop is inactive in NSCs because miR-26b biogenesis is inhibited at the precursor level. Generation of mature miR-26b is activated during neurogenesis, where it suppresses Ctdsp2 protein expression and is required for neuronal cell differentiation in vivo.