Posttranscriptional control of neuronal development by microRNA networks - PubMed (original) (raw)

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Posttranscriptional control of neuronal development by microRNA networks

Fen-Biao Gao. Trends Neurosci. 2008 Jan.

Abstract

The proper development of the nervous system requires precise spatial and temporal control of gene expression at both the transcriptional and translational levels. In different experimental model systems, microRNAs (miRNAs) - a class of small, endogenous, noncoding RNAs that control the translation and stability of many mRNAs - are emerging as important regulators of various aspects of neuronal development. Further dissection of the in vivo physiological functions of individual miRNAs promises to offer novel mechanistic insights into the gene regulatory networks that ensure the precise assembly of a functional nervous system.

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Figures

Figure 1

Figure 1

The roles of miRNAs in the specification of SOPs. In non-SOP cells in the proneural cluster, enhanced Notch signaling leads to the association between Su(H) and Notch intracellular domain (NIntra), which in turn activates the transcription of E(spl). E(spl) suppresses the expression of Sens and proneural genes. To ensure a low level of Sens expression in non-SOP cells, miR-9a suppresses Sens through its 3′ UTR. In SOPs, the lack of Notch signaling leads to the formation of a repressor complex containing Su(H), which inhibits E(spl) expression. Sens expression is high and maintains proneural gene expression that endows the SOP fate. The absence of miR-9a in SOPs is partially responsible for the high level of Sens expression. miR-7 and other miRNAs may be involved in the suppression of E(spl).

Figure 2

Figure 2

Schematic representation of the double negative feedback loops between miRNAs and transcription factors. (a) In ASEL sensory neurons in C. elegans, a high level of lsy-6 suppresses Cog-1, which controls the expression of miR-273. (b) In ASER, a high level of miR-273 suppresses Die-1, a transcription factor required for lsy-6 expression.

Figure 3

Figure 3

The role of miR-124a in neuronal development and its regulation by REST. The upregulation of miR-124a expression during neuronal differentiation requires the derepression by the REST-SCP1 complex. As the most abundant miRNA in the brain, miR-124a regulates the expression of many target mRNAs. Yet, the developmental consequences of lack of miR-124a in vivo remain to be further examined.

Figure 4

Figure 4

A negative feedback loop between an miRNA and a transcription factor in Drosophila. (a) In progenitor cells in the Drosophila eye, high-level expression of the transcription factor Yan suppresses miR-7 expression. (b) During photoreceptor differentiation, transient activation of the epidermal growth factor receptor (EGFR) signaling pathway leads to the degradation of Yan and the expression of miR-7, which further downregulates the level of Yan through binding to its 3′ UTRs.

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