Regulation of neuronal gene expression by local axonal translation

Abstract

RNA localization is a key mechanism in the regulation of protein expression. In neurons, this includes the axonal transport of select mRNAs based on the recognition of axonal localization motifs in these RNAs by RNA binding proteins. Bioinformatic analyses of axonal RNAs suggest that selective inclusion of such localization motifs in mature mRNAs is one mechanism controlling the composition of the axonal transcriptome. The subsequent translation of axonal transcripts in response to specific stimuli provides precise spatiotemporal control of the axonal proteome. This axonal translation supports local phenomena including axon pathfinding, mitochondrial function, and synapse-specific plasticity. Axonal protein synthesis also provides transport machinery and signals for retrograde trafficking to the cell body to effect somatic changes including altering the transcriptional program. Here we review the remarkable progress made in recent years to identify and characterize these phenomena.

Keywords: axon guidance; local translation; mitochondria; retrograde signaling; synapse formation; synaptic plasticity.

Fig. 1

RNA transport and local translation play various roles in axons including: A) Assuring that specific transcripts localize to the correct compartments; B) Supplying growth cones with materials necessary for responding to guidance cues; C) Supporting mitochondrial function; D) Facilitating structural changes underlying synaptic plasticity; and E) Providing proteins that are trafficked back from the axon to the soma during retrograde signaling. Listed are a selection of locally synthesized proteins whose involvement with each step has been characterized.