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Axonal mRNA localization and translation: local events with broad roles

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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.

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Acknowledgements

We thank Andrew P. Hutchins, and members of Ji laboratory for help and comments on the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (31871038, 32170955), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (2021SHIBS0002, 2019SHIBS0002), High-Level University Construction Fund for Department of Biology (internal grant no. G02226301), and Science and Technology Innovation Commission of Shenzhen Municipal Government (ZDSYS20200811144002008).

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SJJ conceived and designed the review. LL, YJ, and SJJ drafted and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sheng-Jian Ji.

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Li, L., Yu, J. & Ji, SJ. Axonal mRNA localization and translation: local events with broad roles. Cell. Mol. Life Sci. 78, 7379–7395 (2021). https://doi.org/10.1007/s00018-021-03995-4

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