Axonal mRNA localization and translation: local events with broad roles - PubMed (original) (raw)

Review

Axonal mRNA localization and translation: local events with broad roles

Lichao Li et al. Cell Mol Life Sci. 2021 Dec.

Abstract

Messenger RNA (mRNA) can be transported and targeted to different subcellular compartments and locally translated. Local translation is an evolutionally conserved mechanism that in mammals, provides an important tool to exquisitely regulate the subcellular proteome in different cell types, including neurons. Local translation in axons is involved in processes such as neuronal development, function, plasticity, and diseases. Here, we summarize the current progress on axonal mRNA transport and translation. We focus on the regulatory mechanisms governing how mRNAs are transported to axons and how they are locally translated in axons. We discuss the roles of axonally synthesized proteins, which either function locally in axons, or are retrogradely trafficked back to soma to achieve neuron-wide gene regulation. We also examine local translation in neurological diseases. Finally, we give a critical perspective on the remaining questions that could be answered to uncover the fundamental rules governing local translation, and discuss how this could lead to new therapeutic targets for neurological diseases.

Keywords: Local protein synthesis; Local translation; Retrograde signaling; mRNA localization; mRNA transport.

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Conflict of interest statement

None of the authors have any competing interests.

Figures

Fig. 1

Regulatory pathways and molecules involved in local translation. a Competitive interactions exist between RBPs and mRNAs. b Mitochondrial proteins are required for NGF-induced local translation of branching-related mRNA and can be inhibited by miR-338. c Translational initiation and elongation factors interact with the cytoskeleton to support local translation. d Slit-2 induces the release of miR-182 from cofilin1 mRNA to activate its translation. e Netrin-1 binds with DCC to induce ribosome dissociation. f BDNF induces phosphorylation of ZBP1 to initiate local translation of β-actin mRNA. g FTO removes m6A modification on GAP-43 mRNA to promote its translation

Fig. 2

Retrograde signaling by axonally synthesized proteins. a Importin β is locally translated and retrogradely transported to the cell body in injured axons. b Axonally synthesized STAT3 is retrogradely transported to nucleus to modulate the survival of injured axons. c Nerve injuries induce local translation of Vimentin, which further facilitates retrograde trafficking of pErk to regulate axon regeneration. d BDNF induces local translation of SMAD1/5/8, which are retrogradely transported to nucleus to regulate neuronal specification. e CREB is locally translated and retrogradely transported to nucleus to promote neuronal survival

References

1. Holt CE, Martin KC, Schuman EM. Local translation in neurons: visualization and function. Nat Struct Mol Biol. 2019;26(7):557–566. - PubMed
1. Holt CE, Bullock SL. Subcellular mRNA localization in animal cells and why it matters. Science. 2009;326(5957):1212–1216. - PMC - PubMed
1. Bassell GJ, Zhang H, Byrd AL, Femino AM, Singer RH, Taneja KL, Lifshitz LM, Herman IM, Kosik KS. Sorting of beta-actin mRNA and protein to neurites and growth cones in culture. J Neurosci. 1998;18(1):251–265. - PMC - PubMed
1. Olink-Coux M, Hollenbeck PJ. Localization and active transport of mRNA in axons of sympathetic neurons in culture. J Neurosci. 1996;16(4):1346–1358. - PMC - PubMed
1. Poulopoulos A, Murphy AJ, Ozkan A, Davis P, Hatch J, Kirchner R, Macklis JD. Subcellular transcriptomes and proteomes of developing axon projections in the cerebral cortex. Nature. 2019;565(7739):356–360. - PMC - PubMed

Axonal mRNA localization and translation: local events with broad roles - PubMed (original) (raw)