In mature neurons, specific targeting of mRNAs to distinct locations within the cytoplasm provides the cell with a very powerful way to rapidly affect the concentration of particular proteins at regions of the neuron quite distal to the nucleus, a particularly important function when the lengths of some neuronal processes can reach several orders of magnitude over the length of the cell soma [31
]. Based on global analyses of mRNA content within the processes of neurons it is clear that not all cellular mRNAs are present at these distal sites [33
]. Because the mRNA content within neurites is not equivalent to the population of mRNA present within the whole cell, it is reasonable to hypothesize that mRNAs are under active sorting mechanisms in the neuronal cytoplasm.
Recruitment of individual mRNAs directly to active synapses has not been demonstrated directly, but many results indicate that synaptic activity influences the distribution of mRNA as well as mRNA binding factors within the processes of neurons [27
]. Several RNA binding proteins demonstrate enrichment within microscopically observable punctate structures, both in fixed cells as well as in living cells using fluorescent protein chimeras [40
]. Fluorescent mRNAs capable of transport into neuronal processes can be found in similar formations after microinjection, and general RNA staining dyes also show punctate staining [42
]. Based on all of these observations, RNPs have been proposed to transport within entities that have been called RNA granules [40
]. The heterogeneous nature of these RNA containing entities within the cytoplasm has made it challenging to gather information on specific mRNA transport pathways by studying them. Despite this, it is abundantly clear that synaptic activity influences the distribution and motility of these entities, and based on this it has been proposed that mRNA localizes to active synapses through the RNA binding factors and activities associated with RNA granules.
Micro RNAs (miRNAs) are a very recent addition to the repertoire of trans
-acting factors that are involved in recognizing mRNA sequence. miRNAs are endogenous small RNAs (21 nt) that have complementarity to sites within subsets of mRNAs and as a result provide sequence specific binding to those mRNAs [44
]. miRNA targeted mRNAs are post-transcriptionally silenced, through translational repression and perhaps enhanced mRNA turnover [45
]. The miRNAs are part of a much larger multi-protein complex, and the mRNA-miRNA interaction functions to target this complex to an mRNA [45
]. Several RNA binding proteins implicated in the transport of mRNA as well as translational control and stability of mRNA have been found among the components of these miRNA-associated complexes [46
]. Moreover, components of miRNA RNP complexes are found in processes and at synapses, and one particular interaction (miR134-Limk1 mRNA) is important for controlling the size of dendritic spines in a synaptic activity sensitive mechanism [47
]. Although it has not been shown that mRNA-miRNA interaction functions to localize mRNAs to the processes of neurons, this is evidence that mRNA-miRNA interactions might repress translation of mRNAs that do get localized.