Competing Interactions of RNA-Binding Proteins, MicroRNAs, and Their Targets Control Neuronal Development and Function.
Competing Interactions of RNA-Binding Proteins, MicroRNAs, and Their Targets Control Neuronal Development and Function.
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DOI：
10.3390/biom5042903
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发表时间：
2015-10-23
期刊：
影响因子：
5.5
通讯作者：
Perrone-Bizzozero NI
中科院分区：
文献类型：
--
作者：
Gardiner AS;Twiss JL;Perrone-Bizzozero NI
转录后机制在神经元发育和成熟过程中的基因表达调控中起着关键作用，因为它们能够对环境信号做出更快的反应，并为蛋白质表达的局部调控提供空间受限的区域。这些机制依赖于mRNA序列中存在的顺式作用元件与反式作用因子的相互作用，例如RNA结合蛋白（RBPs）和微小RNA（miRNAs），它们与这些顺式元件结合并调节mRNA的稳定性、亚细胞定位和翻译。最近的研究揭示了这些相互作用中意想不到的复杂性，其中编码和非编码RNA（被称为竞争性内源RNA，ceRNAs）竞争与miRNAs的结合。这种竞争因此能够控制更多数量的miRNA靶转录本。然而，竞争性RNA网络也延伸到靶mRNA之间对有限数量的RBPs结合的竞争。在这篇综述中，我们提供证据表明靶mRNA之间对RBPs结合的竞争也发生在神经元中，在那里它们影响转录本的稳定性以及向轴突和树突的运输以及翻译。此外，我们通过证明RBPs和miRNAs也竞争靶标结合和调控来说明这些机制的复杂性。
Post-transcriptional mechanisms play critical roles in the control of gene expression during neuronal development and maturation as they allow for faster responses to environmental cues and provide spatially-restricted compartments for local control of protein expression. These mechanisms depend on the interaction of cis-acting elements present in the mRNA sequence and trans-acting factors, such as RNA-binding proteins (RBPs) and microRNAs (miRNAs) that bind to those cis-elements and regulate mRNA stability, subcellular localization, and translation. Recent studies have uncovered an unexpected complexity in these interactions, where coding and non-coding RNAs, termed competing endogenous RNAs (ceRNAs), compete for binding to miRNAs. This competition can, thereby, control a larger number of miRNA target transcripts. However, competing RNA networks also extend to competition between target mRNAs for binding to limited amounts of RBPs. In this review, we present evidence that competitions between target mRNAs for binding to RBPs also occur in neurons, where they affect transcript stability and transport into axons and dendrites as well as translation. In addition, we illustrate the complexity of these mechanisms by demonstrating that RBPs and miRNAs also compete for target binding and regulation.