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Mol Neurobiol (2012) 45:99108 DOI 10.1007/s12035-011-8222-0
Post-Transcriptional Trafficking and Regulation of Neuronal Gene Expression
Belinda J. Goldie & Murray J. Cairns
Received: 19 October 2011 /Accepted: 22 November 2011 /Published online: 14 December 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract Intracellular messenger RNA (mRNA) traffic and translation must be highly regulated, both temporally and spatially, within eukaryotic cells to support the complex functional partitioning. This capacity is essential in neurons because it provides a mechanism for rapid input-restricted activity-dependent protein synthesis in individual dendritic spines. While this feature is thought to be important for synaptic plasticity, the structures and mechanisms that support this capability are largely unknown. Certainly specialized RNA binding proteins and binding elements in the 3 untranslated region (UTR) of translationally regulated mRNA are important, but the subtlety and complexity of this system suggests that an intermediate specificity component is also involved. Small non-coding microRNA (miRNA) are essential for CNS development and may fulfill this role by acting as the guide strand for mediating complex patterns of post-transcriptional regulation. In this review we examine post-synaptic gene regulation, mRNA trafficking and the emerging role of post-transcriptional gene silencing in synaptic plasticity.
Keywords MicroRNA . Gene silencing . Synaptic plasticity. Dendritic spines . Memory
Introduction
Through its network of dendritic and axonal connections, an individual neuron may integrate information from thousands of cells. How it accomplishes this amazing feat of engineering remains a great unknown of neurobiology. What is known is that the establishment of long-term potentiation (LTP) or long-term depression (LTD) at these connections involves a combination of post-translational modification of synaptic protein and subtle changes in gene expression. While real-time changes in protein structure and function are easily reconciled, it is more difficult to imagine how a single transcriptional apparatus could respond to discrete stimuli from so many connections in a timely manner. We now know that to overcome this problem, a significant proportion of activity-associated expression is post-transcriptionally regulated in the dendritic spines of post-synaptic neurons. Understanding how this complex and dynamic temporospatial pattern can be established and encoded in functioning neurons represents a challenging biological problem. In this review, evidence and mechanisms for post-transcriptional regulation of post-synaptic gene expression are examined in the...