Gardiner Amy S, Twiss Jeffery L, Perrone-Bizzozero Nora I
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
Biomolecules. 2015 Oct 23;5(4):2903-18. doi: 10.3390/biom5042903.
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.
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发挥着关键作用，因为它们能够对环境线索做出更快的反应，并为蛋白质表达的局部控制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之间的相互作用，例如与这些顺式元件结合并调节mRNA稳定性、亚细胞定位和翻译的RNA结合蛋白（RBPs）和微小RNA（miRNAs）。最近的研究揭示了这些相互作用中意想不到的复杂性，即编码和非编码RNA，即所谓的竞争性内源RNA（ceRNAs），竞争与miRNAs结合。因此，这种竞争可以控制更多数量的miRNA靶转录本。然而，竞争性RNA网络也扩展到靶mRNA之间竞争结合有限量的RBPs。在这篇综述中，我们提供证据表明，靶mRNA之间竞争结合RBPs的现象也发生在神经元中，这会影响转录本的稳定性、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。
