Abstract
Messenger RNA (mRNA) localization allows spatiotemporal regulation of the proteome at the subcellular level. This is observed in the axons of neurons, where mRNA localization is involved in regulating neuronal development and function by orchestrating rapid adaptive responses to extracellular cues and the maintenance of axonal homeostasis through local translation. Here, we provide an overview of the key findings that have broadened our knowledge regarding how specific mRNAs are trafficked and localize to axons. In particular, we review transcriptomic studies investigating mRNA content in axons and the molecular principles underpinning how these mRNAs arrived there, including cis-acting mRNA sequences and trans-acting proteins playing a role. Further, we discuss evidence that links defective axonal mRNA localization and pathological outcomes.
Highlights
Neurons have the ability to span huge distances across the body
Messenger RNA localization allows spatiotemporal regulation of the proteome at the subcellular level. This is observed in the axons of neurons, where mRNA localization is involved in regulating neuronal development and function by orchestrating rapid adaptive responses to extracellular cues and the maintenance of axonal homeostasis through local translation
It is unambiguously established that mRNA translation in axons is important for neuronal development, function and survival, but our current knowledge of how specific mRNAs become localized to the axonal compartment in the first place remains limited
Summary
The estimated average cumulative length of a human forebrain cholinergic axon is approximately 100 m [1], while the dendritic branches of cat spinal alpha-motor neurons have an average combined length of nearly 5 mm [2] This complex morphology permits the precise connectivity needed to relay and process information across the nervous system. One solution is to traffic particular sets of messenger RNAs (mRNAs) into neuronal processes, where they can be locally translated under basal conditions and in response to particular cues. This approach of localizing mRNAs to axonal and dendritic processes offers several advantages.
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