RNA transport and localized protein synthesis in neurological disorders and neural repair.
Review
Overview
abstract
Neural cells are able to finely tune gene expression through post-transcriptional mechanisms. Localization of mRNAs to subcellular regions has been detected in neurons, oligodendrocytes, and astrocytes providing these domains with a locally renewable source of proteins. Protein synthesis in dendrites has most frequently been associated with synaptic plasticity, while axonally synthesized proteins appear to facilitate pathfinding and injury responses. For oligodendrocytes, mRNAs encoding several proteins for myelin formation are locally generated suggesting that this mechanism assists in myelination. Astrocytic processes have not been well studied but localization of GFAP mRNA has been demonstrated. Both RNA transport and localized translation are regulated processes. RNA transport appears to be highly selective and, at least in part, the destiny of individual mRNAs is determined in the nucleus. RNA-protein and protein-protein interactions determine which mRNAs are targeted to subcellular regions. Several RNA binding proteins that drive mRNA localization have also been shown to repress translation during transport. Activity of the translational machinery is also regulated in distal neural cell processes. Clinically, disruption of mRNA localization and/or localized mRNA translation may contribute to pathophysiology of fragile X mental retardation and spinal muscular atrophy. Axonal injury has been shown to activate localized protein synthesis, providing both a means to initiate regeneration and retrogradely signal injury to the cell body. Decreased capacity to transport mRNAs and translational machinery into distal processes could jeopardize the ability to respond to injury or local stimuli within axons and dendrites.
