Local mRNA translation in long-term maintenance of axon health and function

Abstract

Distal axons, remote from their cell bodies and nuclei, must survive the lifetime of an organism. Recent studies have provided compelling evidence that proteins are locally synthesized in healthy, mature central nervous system axons and presynaptic terminals in vivo. Presynaptic, mitochondrial and ribosomal proteins are locally synthesized in most adult axons of diverse cell types, linking local translation to axon function and survival. Accordingly, inhibiting the intra-axonal translation of key mRNAs or the function of their translational regulators causes dying-back axon degeneration, and human mutations in RNA metabolic pathways are increasingly being associated with neurodegenerative diseases that accompany axon degeneration. Here, we summarize recent relevant findings in a highly simplified 'RNA operon'-based model and discuss open questions and future directions.