Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar;4(1):16-25.
doi: 10.1007/s40142-016-0085-2. Epub 2016 Feb 6.

Regulation of neuronal gene expression by local axonal translation

Affiliations

Regulation of neuronal gene expression by local axonal translation

Lulu I T Korsak et al. Curr Genet Med Rep. 2016 Mar.

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.

PubMed Disclaimer

Figures

Fig. 1
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.

Similar articles

Cited by

References

    1. Kim S, Martin KC. Neuron-wide RNA transport combines with netrin-mediated local translation to spatially regulate the synaptic proteome. eLife. 2015 Feb 4;4:e04158. By investigating how presynaptic translation can be limited specifically to activated synapses despite broad distribution of presynaptic RNAs, this study identified that postsynaptic activity induces calcium-dependent release of netrin. This netrin binds to its presynaptic receptor to induce local translation only at activated synapses. - PMC - PubMed
    1. Andreassi C, Zimmermann C, Mitter R, Fusco S, De Vita S, Devita S, et al. An NGF-responsive element targets myo-inositol monophosphatase-1 mRNA to sympathetic neuron axons. Nat Neurosci. 2010 Mar;13(3):291–301. - PubMed
    1. Baleriola J, Walker CA, Jean YY, Crary JF, Troy CM, Nagy PL, et al. Axonally Synthesized ATF4 Transmits a Neurodegenerative Signal across Brain Regions. Cell. 2014 Aug 28;158(5):1159–72. Alzheimer’s pathology appears to spread over long distances between brain regions that are connected with each other. This paper reveals that axon exposure to pathogenic Aβ oligomers induces the axonal transport and subsequent axonal translation of transcripts that can induce neurodegeneration. - PMC - PubMed
    1. Merianda TT, Coleman J, Kim HH, Kumar Sahoo P, Gomes C, Brito-Vargas P, et al. Axonal amphoterin mRNA is regulated by translational control and enhances axon outgrowth. J Neurosci. 2015 Apr 8;35(14):5693–706. - PMC - PubMed
    1. Kislauskis EH, Zhu X, Singer RH. Sequences responsible for intracellular localization of beta-actin messenger RNA also affect cell phenotype. J Cell Biol. 1994 Oct 15;127(2):441–51. - PMC - PubMed

LinkOut - more resources