A Proposed Role for Interactions between Argonautes, miRISC, and RNA Binding Proteins in the Regulation of Local Translation in Neurons and Glia

Abstract

The first evidence of local translation in the CNS appeared nearly 40 years ago, when electron microscopic studies showed polyribosomes localized to the base of dendritic spines. Since then, local translation has been established as an important regulatory mechanism for gene expression in polarized or functionally compartmentalized cells. While much attention has been placed on characterizing the local transcriptome and regulatory “grammar” directing mRNA localization in neurons and glia, less is understood about how these cells subsequently de-repress mRNA translation in their peripheral processes to produce a rapid translational response to stimuli. MicroRNA-mediated translation regulation offers a possible solution to this question. Not only do miRNAs provide the specificity needed for targeted gene regulation, but association and dynamic interactions between Argonaute (AGO) with sequence-specific RNA-binding proteins may provide a molecular switch to allow for de-repression of target mRNAs. Here, we review the expression and activity of different AGO proteins in miRNA-induced silencing complexes in neurons and glia and discuss known pathways of miRNA-mediated regulation, including activity-dependent pre-miRNA maturation in dendrites. We further detail work on AGO and RNA-binding protein interactions that allow for the reversal of miRNA-mediated translational silencing, and we propose a model for how intercellular communication may play a role in the regulation of local translation.